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in the Absence of CD4 T Cells Fully Functional Memory CD8 T Cells

2000

173:969-975; ; J Immunol References http://www.jimmunol.org/content/173/2/969.full#ref-list-1 , 24 of which you can access for free at: cites 41 articles This article Subscriptions http://jimmunol.org/subscriptions is online at: The Journal of Immunology Information about subscribing to

Expression of CD8? identifies a distinct subset of effector memory CD4 + T lymphocytes

Immunology, 2006

Circulating CD4 + CD8 + T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4 + CD8 + T cells in rhesus macaques. Two distinct populations of CD4 + CD8 + T cells were identified: the dominant one was CD4 hi CD8 lo and expressed the CD8aa homodimer, while the minor population was CD4 lo CD8 hi and expressed the CD8ab heterodimer. The majority of CD4 hi CD8a lo T cells exhibited an activated effector/memory phenotype (CCR5 lo CD7-CD28-HLA-DR +) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4 hi CD8a lo T cells compared to single-positive CD4 + T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4 hi CD8a lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4 hi CD8a lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4 + T cells expressing CD8a represent an effector/memory subset of CD4 + T cells and that this cell population can be depleted during the course of SIV infection.

Expression of CD8? identifies a distinct subset of effector memory CD4+T lymphocytes

Immunology, 2006

Circulating CD4 + CD8 + T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4 + CD8 + T cells in rhesus macaques. Two distinct populations of CD4 + CD8 + T cells were identified: the dominant one was CD4 hi CD8 lo and expressed the CD8aa homodimer, while the minor population was CD4 lo CD8 hi and expressed the CD8ab heterodimer. The majority of CD4 hi CD8a lo T cells exhibited an activated effector/memory phenotype (CCR5 lo CD7-CD28-HLA-DR +) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4 hi CD8a lo T cells compared to single-positive CD4 + T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4 hi CD8a lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4 hi CD8a lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4 + T cells expressing CD8a represent an effector/memory subset of CD4 + T cells and that this cell population can be depleted during the course of SIV infection.

Fully Functional Memory CD8 T Cells in the Absence of CD4 T Cells

The Journal of Immunology, 2004

173:969-975; ; J Immunol References http://www.jimmunol.org/content/173/2/969.full#ref-list-1 , 24 of which you can access for free at: cites 41 articles This article Subscriptions http://jimmunol.org/subscriptions is online at: The Journal of Immunology Information about subscribing to

Human CD8+ and CD4+ T Cell Memory to Lymphocytic Choriomeningitis Virus Infection

Journal of Virology, 2011

understood. Thus, we analyzed the breadths, magnitudes, and differentiation phenotypes of memory LCMVspecific CD8 ؉ and CD4 ؉ T cells in three human donors displaying a variety of disease outcomes after accidental needle stick injury or exposure to LCMV. Although only a small cohort of donors was analyzed at a single time point postinfection, several interesting observations were made. First, we were able to detect LCMV-specific CD8 ؉ and CD4 ؉ T cell responses directly ex vivo at 4 to 8 years after exposure, demonstrating the longevity of T cell memory in humans. Second, unlike in murine models of LCMV infection, we found that the breadths of memory CD8 ؉ and CD4 ؉ T cell responses were not significantly different from one another. Third, it seemed that the overall CD8 ؉ T cell response was augmented with increasing severity of disease, while the LCMV-specific CD4 ؉ T cell response magnitude was highly variable between the three different donors. Next, we found that LCMV-specific CD8 ؉ T cells in the three donors analyzed seemed to undergo an effector memory differentiation program distinct from that of CD4 ؉ T cells. Finally, the levels of expression of memory, costimulatory, and inhibitory receptors on CD8 ؉ and CD4 ؉ T cell subsets, in some instances, correlated with disease outcome. These data demonstrate for the first time LCMV-specific CD8 ؉ and CD4 ؉ T cells in infected humans and begin to provide new insights into memory T cell responses following an acute virus infection.

Independent Regulation of Lymphocytic Choriomeningitis Virus-Specific T Cell Memory Pools: Relative Stability of CD4 Memory Under Conditions of CD8 Memory T Cell Loss

The Journal of Immunology, 2001

Infection of mice with a series of heterologous viruses causes a reduction of memory CD8 ؉ T cells specific to viruses from earlier infections, but the fate of the virus-specific memory CD4 ؉ T cell pool following multiple virus infections has been unknown. We have previously reported that the virus-specific CD4 ؉ Th precursor (Thp) frequency remains stable into long-term immunity following lymphocytic choriomeningitis virus (LCMV) infection. In this study, we questioned whether heterologous virus infections or injection with soluble protein CD4 Ags would impact this stable LCMV-specific CD4 ؉ Thp memory pool. Limiting dilution analyses for IL-2-producing cells and intracellular cytokine staining for IFN-␥ revealed that the LCMV-specific CD4 ؉ Thp frequency remains relatively stable following multiple heterologous virus infections or protein Ag immunizations, even under conditions that dramatically reduce the LCMV-specific CD8 ؉ CTL precursor frequency. These data indicate that the CD4 ؉ and CD8 ؉ memory T cell pools are regulated independently and that the loss in CD8 ؉ T cell memory following heterologous virus infections is not a consequence of a parallel loss in the memory CD4 ؉ T cell population.