gabriela diaz - Academia.edu (original) (raw)
Papers by gabriela diaz
Journal of Virology, 2002
The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of s... more The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b؉/؉ and CD4 ؉ -T-cell-deficient I-A b؊/؊ mice. Comparable levels of virus-specific cytotoxic-Tlymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 ؉ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b؊/؊ mice. Thus, though the capacity to mediate the CD8 ؉ -T-cell effector function is broadly preserved in the absence of concurrent CD4 ؉ -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.
Immunity, 2003
The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell r... more The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell responses in mice with influenza pneumonia. Single-cell RT-PCR established that the same clonotypes were present in the lymphoid tissue and in the virus-infected lung. Longitudinal analysis indicated that the memory TCR repertoire reflects the primary response, with no decrease in diversity prior to (or after) secondary challenge. The re-engagement of memory T cells looked to be stochastic in this localized, transient infection. Analysis of clonotypes from the blood, spleen, regional lymph nodes, bone marrow, lung, and liver over a 200 day interval showed no evidence of selective localization or loss. The long-term distribution of memory T cells seemed to be essentially random.
Journal of Virology, 2002
The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of s... more The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b؉/؉ and CD4 ؉ -T-cell-deficient I-A b؊/؊ mice. Comparable levels of virus-specific cytotoxic-Tlymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 ؉ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b؊/؊ mice. Thus, though the capacity to mediate the CD8 ؉ -T-cell effector function is broadly preserved in the absence of concurrent CD4 ؉ -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.
Journal of Virology, 2003
The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been a... more The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [␥HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 ؉ T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with ␥HV68, though the prior presence of a large CD8 ؉ D b NP 366 ؉ population caused no selective defect in the ␥HV68-specific CD8 ؉ K b p79 ؉ response. Conversely, mice that had been primed and boosted to generate substantial ␥HV68-specific CD8 ؉ D b p56 ؉ populations did not show any decrease in prevalence for this set of CD8 ؉ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8 ؉ -T-cell pool was significantly diminished in those that had been infected with ␥HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.
Immunity, 2003
The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell r... more The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell responses in mice with influenza pneumonia. Single-cell RT-PCR established that the same clonotypes were present in the lymphoid tissue and in the virus-infected lung. Longitudinal analysis indicated that the memory TCR repertoire reflects the primary response, with no decrease in diversity prior to (or after) secondary challenge. The re-engagement of memory T cells looked to be stochastic in this localized, transient infection. Analysis of clonotypes from the blood, spleen, regional lymph nodes, bone marrow, lung, and liver over a 200 day interval showed no evidence of selective localization or loss. The long-term distribution of memory T cells seemed to be essentially random.
Journal of Virology, 2002
The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of s... more The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b؉/؉ and CD4 ؉ -T-cell-deficient I-A b؊/؊ mice. Comparable levels of virus-specific cytotoxic-Tlymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 ؉ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b؊/؊ mice. Thus, though the capacity to mediate the CD8 ؉ -T-cell effector function is broadly preserved in the absence of concurrent CD4 ؉ -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.
Journal of Virology, 2003
The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been a... more The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [␥HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 ؉ T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with ␥HV68, though the prior presence of a large CD8 ؉ D b NP 366 ؉ population caused no selective defect in the ␥HV68-specific CD8 ؉ K b p79 ؉ response. Conversely, mice that had been primed and boosted to generate substantial ␥HV68-specific CD8 ؉ D b p56 ؉ populations did not show any decrease in prevalence for this set of CD8 ؉ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8 ؉ -T-cell pool was significantly diminished in those that had been infected with ␥HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.
Immunity, 2003
The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell r... more The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell responses in mice with influenza pneumonia. Single-cell RT-PCR established that the same clonotypes were present in the lymphoid tissue and in the virus-infected lung. Longitudinal analysis indicated that the memory TCR repertoire reflects the primary response, with no decrease in diversity prior to (or after) secondary challenge. The re-engagement of memory T cells looked to be stochastic in this localized, transient infection. Analysis of clonotypes from the blood, spleen, regional lymph nodes, bone marrow, lung, and liver over a 200 day interval showed no evidence of selective localization or loss. The long-term distribution of memory T cells seemed to be essentially random.
Journal of Virology, 2003
The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been a... more The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [␥HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 ؉ T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with ␥HV68, though the prior presence of a large CD8 ؉ D b NP 366 ؉ population caused no selective defect in the ␥HV68-specific CD8 ؉ K b p79 ؉ response. Conversely, mice that had been primed and boosted to generate substantial ␥HV68-specific CD8 ؉ D b p56 ؉ populations did not show any decrease in prevalence for this set of CD8 ؉ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8 ؉ -T-cell pool was significantly diminished in those that had been infected with ␥HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.
Journal of Virology, 2002
The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of s... more The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b؉/؉ and CD4 ؉ -T-cell-deficient I-A b؊/؊ mice. Comparable levels of virus-specific cytotoxic-Tlymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 ؉ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b؊/؊ mice. Thus, though the capacity to mediate the CD8 ؉ -T-cell effector function is broadly preserved in the absence of concurrent CD4 ؉ -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.
Immunity, 2003
The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell r... more The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell responses in mice with influenza pneumonia. Single-cell RT-PCR established that the same clonotypes were present in the lymphoid tissue and in the virus-infected lung. Longitudinal analysis indicated that the memory TCR repertoire reflects the primary response, with no decrease in diversity prior to (or after) secondary challenge. The re-engagement of memory T cells looked to be stochastic in this localized, transient infection. Analysis of clonotypes from the blood, spleen, regional lymph nodes, bone marrow, lung, and liver over a 200 day interval showed no evidence of selective localization or loss. The long-term distribution of memory T cells seemed to be essentially random.
Journal of Virology, 2003
The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been a... more The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [␥HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 ؉ T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with ␥HV68, though the prior presence of a large CD8 ؉ D b NP 366 ؉ population caused no selective defect in the ␥HV68-specific CD8 ؉ K b p79 ؉ response. Conversely, mice that had been primed and boosted to generate substantial ␥HV68-specific CD8 ؉ D b p56 ؉ populations did not show any decrease in prevalence for this set of CD8 ؉ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8 ؉ -T-cell pool was significantly diminished in those that had been infected with ␥HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.
Journal of Virology, 2002
The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of s... more The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b؉/؉ and CD4 ؉ -T-cell-deficient I-A b؊/؊ mice. Comparable levels of virus-specific cytotoxic-Tlymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 ؉ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b؊/؊ mice. Thus, though the capacity to mediate the CD8 ؉ -T-cell effector function is broadly preserved in the absence of concurrent CD4 ؉ -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.
Immunity, 2003
The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell r... more The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell responses in mice with influenza pneumonia. Single-cell RT-PCR established that the same clonotypes were present in the lymphoid tissue and in the virus-infected lung. Longitudinal analysis indicated that the memory TCR repertoire reflects the primary response, with no decrease in diversity prior to (or after) secondary challenge. The re-engagement of memory T cells looked to be stochastic in this localized, transient infection. Analysis of clonotypes from the blood, spleen, regional lymph nodes, bone marrow, lung, and liver over a 200 day interval showed no evidence of selective localization or loss. The long-term distribution of memory T cells seemed to be essentially random.
Journal of Virology, 2002
The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of s... more The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b؉/؉ and CD4 ؉ -T-cell-deficient I-A b؊/؊ mice. Comparable levels of virus-specific cytotoxic-Tlymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 ؉ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b؊/؊ mice. Thus, though the capacity to mediate the CD8 ؉ -T-cell effector function is broadly preserved in the absence of concurrent CD4 ؉ -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.
Journal of Virology, 2003
The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been a... more The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [␥HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 ؉ T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with ␥HV68, though the prior presence of a large CD8 ؉ D b NP 366 ؉ population caused no selective defect in the ␥HV68-specific CD8 ؉ K b p79 ؉ response. Conversely, mice that had been primed and boosted to generate substantial ␥HV68-specific CD8 ؉ D b p56 ؉ populations did not show any decrease in prevalence for this set of CD8 ؉ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8 ؉ -T-cell pool was significantly diminished in those that had been infected with ␥HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.
Immunity, 2003
The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell r... more The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell responses in mice with influenza pneumonia. Single-cell RT-PCR established that the same clonotypes were present in the lymphoid tissue and in the virus-infected lung. Longitudinal analysis indicated that the memory TCR repertoire reflects the primary response, with no decrease in diversity prior to (or after) secondary challenge. The re-engagement of memory T cells looked to be stochastic in this localized, transient infection. Analysis of clonotypes from the blood, spleen, regional lymph nodes, bone marrow, lung, and liver over a 200 day interval showed no evidence of selective localization or loss. The long-term distribution of memory T cells seemed to be essentially random.
Journal of Virology, 2002
The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of s... more The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b؉/؉ and CD4 ؉ -T-cell-deficient I-A b؊/؊ mice. Comparable levels of virus-specific cytotoxic-Tlymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 ؉ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b؊/؊ mice. Thus, though the capacity to mediate the CD8 ؉ -T-cell effector function is broadly preserved in the absence of concurrent CD4 ؉ -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.
Journal of Virology, 2003
The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been a... more The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [␥HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 ؉ T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with ␥HV68, though the prior presence of a large CD8 ؉ D b NP 366 ؉ population caused no selective defect in the ␥HV68-specific CD8 ؉ K b p79 ؉ response. Conversely, mice that had been primed and boosted to generate substantial ␥HV68-specific CD8 ؉ D b p56 ؉ populations did not show any decrease in prevalence for this set of CD8 ؉ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8 ؉ -T-cell pool was significantly diminished in those that had been infected with ␥HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.
Immunity, 2003
The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell r... more The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell responses in mice with influenza pneumonia. Single-cell RT-PCR established that the same clonotypes were present in the lymphoid tissue and in the virus-infected lung. Longitudinal analysis indicated that the memory TCR repertoire reflects the primary response, with no decrease in diversity prior to (or after) secondary challenge. The re-engagement of memory T cells looked to be stochastic in this localized, transient infection. Analysis of clonotypes from the blood, spleen, regional lymph nodes, bone marrow, lung, and liver over a 200 day interval showed no evidence of selective localization or loss. The long-term distribution of memory T cells seemed to be essentially random.
Journal of Virology, 2003
The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been a... more The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [␥HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 ؉ T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with ␥HV68, though the prior presence of a large CD8 ؉ D b NP 366 ؉ population caused no selective defect in the ␥HV68-specific CD8 ؉ K b p79 ؉ response. Conversely, mice that had been primed and boosted to generate substantial ␥HV68-specific CD8 ؉ D b p56 ؉ populations did not show any decrease in prevalence for this set of CD8 ؉ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8 ؉ -T-cell pool was significantly diminished in those that had been infected with ␥HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.
Journal of Virology, 2002
The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of s... more The primary influenza A virus-specific CD8 ؉ -T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-A b؉/؉ and CD4 ؉ -T-cell-deficient I-A b؊/؊ mice. Comparable levels of virus-specific cytotoxic-Tlymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4 ؉ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-A b؊/؊ mice. Thus, though the capacity to mediate the CD8 ؉ -T-cell effector function is broadly preserved in the absence of concurrent CD4 ؉ -T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.
Immunity, 2003
The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell r... more The spectrum of TCR V beta usage is compared for primary and recall CD8(+)D(b)PA(224)(+) T cell responses in mice with influenza pneumonia. Single-cell RT-PCR established that the same clonotypes were present in the lymphoid tissue and in the virus-infected lung. Longitudinal analysis indicated that the memory TCR repertoire reflects the primary response, with no decrease in diversity prior to (or after) secondary challenge. The re-engagement of memory T cells looked to be stochastic in this localized, transient infection. Analysis of clonotypes from the blood, spleen, regional lymph nodes, bone marrow, lung, and liver over a 200 day interval showed no evidence of selective localization or loss. The long-term distribution of memory T cells seemed to be essentially random.
Journal of Virology, 2003
The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been a... more The consequences for the long-term maintenance of virus-specific CD8 ؉ -T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [␥HV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8 ؉ T cells specific for the prominent influenza virus D b NP 366 epitope were reduced by about half in mice that had been challenged 100 days previously with ␥HV68, though the prior presence of a large CD8 ؉ D b NP 366 ؉ population caused no selective defect in the ␥HV68-specific CD8 ؉ K b p79 ؉ response. Conversely, mice that had been primed and boosted to generate substantial ␥HV68-specific CD8 ؉ D b p56 ؉ populations did not show any decrease in prevalence for this set of CD8 ؉ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8 ؉ -T-cell pool was significantly diminished in those that had been infected with ␥HV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory "phenome" is a function of the overall infection experience of the individual.