Jeanette Boudreau | McMaster University (original) (raw)

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Papers by Jeanette Boudreau

Research paper thumbnail of Enhanced Antitumor Immunity Elicited by Dendritic Cell Vaccines Is a Result of Their Ability to Engage Both CTL and IFNγ-Producing NK Cells

Research paper thumbnail of Recombinant Vesicular Stomatitis Virus Transduction of Dendritic Cells Enhances Their Ability to Prime Innate and Adaptive Antitumor Immunity

Molecular …, Jan 1, 2009

Dendritic cell (DC)-based vaccines are a promising strategy for tumor immunotherapy due to their ... more Dendritic cell (DC)-based vaccines are a promising strategy for tumor immunotherapy due to their ability to activate both antigen-specific T-cell immunity and innate immune effector components, including natural killer (NK) cells. However, the optimal mode of antigen delivery and DC activation remains to be determined. Using M protein mutant vesicular stomatitis virus (DeltaM51-VSV) as a gene-delivery vector, we demonstrate that a high level of transgene expression could be achieved in approximately 70% of DCs without affecting cell viability. Furthermore, DeltaM51-VSV infection activated DCs to produce proinflammatory cytokines (interleukin-12, tumor necrosis factor-alpha, and interferon (IFN)alpha/beta), and to display a mature phenotype (CD40(high)CD86(high) major histocompatibility complex (MHC II)(high)). When delivered to mice bearing 10-day-old lung metastatic tumors, DCs infected with DeltaM51-VSV encoding a tumor-associated antigen mediated significant control of tumor growth by engaging both NK and CD8(+) T cells. Importantly, depletion of NK cells completely abrogated tumor destruction, indicating that NK cells play a critical role for this DC vaccine-induced therapeutic outcome. Our findings identify DeltaM51-VSV as both an efficient gene-delivery vector and a maturation agent allowing DC vaccines to overcome immunosuppression in the tumor-bearing host.

Research paper thumbnail of Voluntary Training In Mice and Submandibular Lymphocyte Response to Acute Exercise

Medicine & Science in …, Jan 1, 2005

Submandibular lymph nodes (SLN) are important for immune responses to antigens in the eye and ora... more Submandibular lymph nodes (SLN) are important for immune responses to antigens in the eye and oral mucosa. Athletes and exercise participants may be at increased risk of ocular, oral, and upper respiratory tract infections. This study was conducted to examine the effects of voluntary training on the distribution, number, and apoptotic status of SLN lymphocytes in response to an acute bout of strenuous exercise. Female C57BL/6 mice were assigned to voluntary wheel-running (WR) exercise (N=20) or were sedentary (N=10) for 16 wk. SLN lymphocytes were examined immediately (EX+Imm) or 24 h (EX+24 h) following strenuous treadmill exercise, or exposure to treadmill conditions without running (NonEX). Intracellular glutathione (GSH), mitochondrial membrane potential (MMP), cell viability (propidium iodide uptake, PI), surface phosphatidylserine (Annexin V), T-lymphocyte (CD3, CD4, CD8), and B-lymphocyte (CD19) phenotype distribution and number were assessed. The WR mice had a higher number and percent CD8 SLN lymphocytes, higher MMP, and lower Annexin V/PI SLN lymphocytes than controls. Regardless of training status, an acute bout of strenuous exercise decreased the total and phenotype specific (CD3, CD4, CD8) number of cells, MMP, and GSH levels immediately after exercise. WR in mice improved some aspects of cell viability in SLN lymphocytes compared with controls, but did not prevent the transient cell loss after acute treadmill exercise. Given the depletion in intracellular GSH levels, oxidative stress may account for the decline in SLN lymphocyte numbers following acute exercise. Loss of SLN lymphocytes may have consequences for ocular, oral, and upper respiratory tract health in some exercise participants and athletes during periods of overtraining.

Research paper thumbnail of Vesicular Stomatitis Virus As a Novel Cancer Vaccine Vector to Prime Antitumor Immunity Amenable to Rapid Boosting With Adenovirus

Research paper thumbnail of D-and L-enantiomers of 2-and 6-FDOPA for melanoma imaging

Society of Nuclear …, Jan 1, 2009

Research paper thumbnail of Adaptive Antiviral Immunity Is a Determinant of the Therapeutic Success of Oncolytic Virotherapy

Research paper thumbnail of Adrenalectomy Does Not Prevent Exercise-Induced Intestinal Lymphocyte Depletion Following Treadmill Exercise In Mice

Medicine & Science …, Jan 1, 2004

Research paper thumbnail of IL-15 AND TYPE I INTERFERON ARE REQUIRED FOR ACTIVATION OF TUMORICIDAL NK CELLS BY VIRUS-INFECTED DENDRITIC CELLS

Cancer Research, Jan 1, 2011

Research paper thumbnail of Potentiating Cancer Immunotherapy Using an Oncolytic Virus

Research paper thumbnail of CD8+ T-cell expansion and maintenance after recombinant adenovirus immunization rely upon cooperation between hematopoietic and nonhematopoietic antigen- …

…, Jan 1, 2011

We have recently reported that CD8(+) T-cell memory maintenance after immunization with recombina... more We have recently reported that CD8(+) T-cell memory maintenance after immunization with recombinant human adenovirus type 5 (rHuAd5) is dependent upon persistent transgene expression beyond the peak of the response. In this report, we have further investigated the location and nature of the cell populations responsible for this sustained response. The draining lymph nodes were found to be important for primary expansion but not for memory maintenance, suggesting that antigen presentation through a nonlymphoid source was required. Using bone marrow chimeric mice, we determined that antigen presentation by nonhematopoietic antigen-presenting cells (APCs) was sufficient for maintenance of CD8(+) T-cell numbers. However, antigen presentation by this mechanism alone yielded a memory population that displayed alterations in phenotype, cytokine production and protective capacity, indicating that antigen presentation through both hematopoietic and nonhematopoietic APCs ultimately defines the memory CD8(+) T-cell response produced by rHuAd5. These results shed new light on the immunobiology of rHuAd5 vectors and provide evidence for a mechanism of CD8(+) T-cell expansion and memory maintenance that relies upon both hematopoietic and nonhematopoietic APCs.

Research paper thumbnail of Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

Journal of Applied …, Jan 1, 2004

Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocy... more Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocyte apoptosis, and a reduction in intestinal lymphocyte number. The present study examined the role of GCs on the numerical changes seen in intestinal lymphocytes after exercise. Female C57BL/6 mice were bilaterally adrenalectomized (ADX; n = 18) or given sham surgery (Sham; n = 18) and assigned to one of three exercise conditions: treadmill running (28 m/min, 90 min, 2 degrees slope) and killed immediately or after 24 h recovery, or not exercised and killed immediately after 90-min exposure to the treadmill environment. Lymphocytes were isolated from the intestines with CD45(+) cells collected by positive selection using magnetic bead separation columns, and lymphocyte subpopulations were analyzed by flow cytometry for CD45(+), CD3alphabeta(+), CD3gammadelta(+), CD8beta(+), CD8alpha(+), CD4(+), and NK(+) phenotypic markers. ADX mice had significantly more intestinal CD45(+) leukocytes (P < 0.05) and CD3alphabeta(+) (P < 0.05), CD3gammadelta(+) (P < 0.01), CD8alpha(+) (P < 0.001), and NK(+) (P < 0.05) intestinal lymphocytes than Sham mice. There was a significant effect of exercise condition on total intestinal CD45(+) leukocytes (P < 0.01) and CD3alphabeta(+) (P < 0.05), CD8alpha(+) (P < 0.001), and CD4(+) (P < 0.05) intestinal lymphocytes, with fewer cells at 24 h postexercise compared with the other treatment conditions. There were no surgical x exercise interaction effects on the CD3 and CD8 phenotype numbers. Plasma corticosterone was virtually nil in ADX mice regardless of exercise condition but was significantly elevated in Sham mice immediately postexercise (P < 0.001). The data indicate that ADX does not prevent the loss of lymphocytes from the intestinal mucosa 24 h after strenuous exercise and GCs are not directly causal in the leukopenia of exercise.

Research paper thumbnail of Lymphocyte distribution in mouse submandibular lymph nodes in response to acute treadmill exercise

Canadian journal of …, Jan 1, 2003

Research paper thumbnail of Polyethylene glycol but not mifepristone prevents intestinal lymphocyte loss following treadmill exercise in mice

Acta Physiologica …, Jan 1, 2005

Research paper thumbnail of Long-duration freewheel running and submandibular lymphocyte response to forced exercise in older mice

Canadian journal of …, Jan 1, 2006

Abstract: Submandibular lymph nodes (SLN) are crucial for immune surveillance of the anterior ocu... more Abstract: Submandibular lymph nodes (SLN) are crucial for immune surveillance of the anterior ocular chamber and upper respiratory tract; little is known about how training and exercise affect SLN lymphocytes. The intent of this study was to describe the impact of long term ...

Research paper thumbnail of Enhanced Antitumor Immunity Elicited by Dendritic Cell Vaccines Is a Result of Their Ability to Engage Both CTL and IFNγ-Producing NK Cells

Research paper thumbnail of Recombinant Vesicular Stomatitis Virus Transduction of Dendritic Cells Enhances Their Ability to Prime Innate and Adaptive Antitumor Immunity

Molecular …, Jan 1, 2009

Dendritic cell (DC)-based vaccines are a promising strategy for tumor immunotherapy due to their ... more Dendritic cell (DC)-based vaccines are a promising strategy for tumor immunotherapy due to their ability to activate both antigen-specific T-cell immunity and innate immune effector components, including natural killer (NK) cells. However, the optimal mode of antigen delivery and DC activation remains to be determined. Using M protein mutant vesicular stomatitis virus (DeltaM51-VSV) as a gene-delivery vector, we demonstrate that a high level of transgene expression could be achieved in approximately 70% of DCs without affecting cell viability. Furthermore, DeltaM51-VSV infection activated DCs to produce proinflammatory cytokines (interleukin-12, tumor necrosis factor-alpha, and interferon (IFN)alpha/beta), and to display a mature phenotype (CD40(high)CD86(high) major histocompatibility complex (MHC II)(high)). When delivered to mice bearing 10-day-old lung metastatic tumors, DCs infected with DeltaM51-VSV encoding a tumor-associated antigen mediated significant control of tumor growth by engaging both NK and CD8(+) T cells. Importantly, depletion of NK cells completely abrogated tumor destruction, indicating that NK cells play a critical role for this DC vaccine-induced therapeutic outcome. Our findings identify DeltaM51-VSV as both an efficient gene-delivery vector and a maturation agent allowing DC vaccines to overcome immunosuppression in the tumor-bearing host.

Research paper thumbnail of Voluntary Training In Mice and Submandibular Lymphocyte Response to Acute Exercise

Medicine & Science in …, Jan 1, 2005

Submandibular lymph nodes (SLN) are important for immune responses to antigens in the eye and ora... more Submandibular lymph nodes (SLN) are important for immune responses to antigens in the eye and oral mucosa. Athletes and exercise participants may be at increased risk of ocular, oral, and upper respiratory tract infections. This study was conducted to examine the effects of voluntary training on the distribution, number, and apoptotic status of SLN lymphocytes in response to an acute bout of strenuous exercise. Female C57BL/6 mice were assigned to voluntary wheel-running (WR) exercise (N=20) or were sedentary (N=10) for 16 wk. SLN lymphocytes were examined immediately (EX+Imm) or 24 h (EX+24 h) following strenuous treadmill exercise, or exposure to treadmill conditions without running (NonEX). Intracellular glutathione (GSH), mitochondrial membrane potential (MMP), cell viability (propidium iodide uptake, PI), surface phosphatidylserine (Annexin V), T-lymphocyte (CD3, CD4, CD8), and B-lymphocyte (CD19) phenotype distribution and number were assessed. The WR mice had a higher number and percent CD8 SLN lymphocytes, higher MMP, and lower Annexin V/PI SLN lymphocytes than controls. Regardless of training status, an acute bout of strenuous exercise decreased the total and phenotype specific (CD3, CD4, CD8) number of cells, MMP, and GSH levels immediately after exercise. WR in mice improved some aspects of cell viability in SLN lymphocytes compared with controls, but did not prevent the transient cell loss after acute treadmill exercise. Given the depletion in intracellular GSH levels, oxidative stress may account for the decline in SLN lymphocyte numbers following acute exercise. Loss of SLN lymphocytes may have consequences for ocular, oral, and upper respiratory tract health in some exercise participants and athletes during periods of overtraining.

Research paper thumbnail of Vesicular Stomatitis Virus As a Novel Cancer Vaccine Vector to Prime Antitumor Immunity Amenable to Rapid Boosting With Adenovirus

Research paper thumbnail of D-and L-enantiomers of 2-and 6-FDOPA for melanoma imaging

Society of Nuclear …, Jan 1, 2009

Research paper thumbnail of Adaptive Antiviral Immunity Is a Determinant of the Therapeutic Success of Oncolytic Virotherapy

Research paper thumbnail of Adrenalectomy Does Not Prevent Exercise-Induced Intestinal Lymphocyte Depletion Following Treadmill Exercise In Mice

Medicine & Science …, Jan 1, 2004

Research paper thumbnail of IL-15 AND TYPE I INTERFERON ARE REQUIRED FOR ACTIVATION OF TUMORICIDAL NK CELLS BY VIRUS-INFECTED DENDRITIC CELLS

Cancer Research, Jan 1, 2011

Research paper thumbnail of Potentiating Cancer Immunotherapy Using an Oncolytic Virus

Research paper thumbnail of CD8+ T-cell expansion and maintenance after recombinant adenovirus immunization rely upon cooperation between hematopoietic and nonhematopoietic antigen- …

…, Jan 1, 2011

We have recently reported that CD8(+) T-cell memory maintenance after immunization with recombina... more We have recently reported that CD8(+) T-cell memory maintenance after immunization with recombinant human adenovirus type 5 (rHuAd5) is dependent upon persistent transgene expression beyond the peak of the response. In this report, we have further investigated the location and nature of the cell populations responsible for this sustained response. The draining lymph nodes were found to be important for primary expansion but not for memory maintenance, suggesting that antigen presentation through a nonlymphoid source was required. Using bone marrow chimeric mice, we determined that antigen presentation by nonhematopoietic antigen-presenting cells (APCs) was sufficient for maintenance of CD8(+) T-cell numbers. However, antigen presentation by this mechanism alone yielded a memory population that displayed alterations in phenotype, cytokine production and protective capacity, indicating that antigen presentation through both hematopoietic and nonhematopoietic APCs ultimately defines the memory CD8(+) T-cell response produced by rHuAd5. These results shed new light on the immunobiology of rHuAd5 vectors and provide evidence for a mechanism of CD8(+) T-cell expansion and memory maintenance that relies upon both hematopoietic and nonhematopoietic APCs.

Research paper thumbnail of Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

Journal of Applied …, Jan 1, 2004

Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocy... more Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocyte apoptosis, and a reduction in intestinal lymphocyte number. The present study examined the role of GCs on the numerical changes seen in intestinal lymphocytes after exercise. Female C57BL/6 mice were bilaterally adrenalectomized (ADX; n = 18) or given sham surgery (Sham; n = 18) and assigned to one of three exercise conditions: treadmill running (28 m/min, 90 min, 2 degrees slope) and killed immediately or after 24 h recovery, or not exercised and killed immediately after 90-min exposure to the treadmill environment. Lymphocytes were isolated from the intestines with CD45(+) cells collected by positive selection using magnetic bead separation columns, and lymphocyte subpopulations were analyzed by flow cytometry for CD45(+), CD3alphabeta(+), CD3gammadelta(+), CD8beta(+), CD8alpha(+), CD4(+), and NK(+) phenotypic markers. ADX mice had significantly more intestinal CD45(+) leukocytes (P < 0.05) and CD3alphabeta(+) (P < 0.05), CD3gammadelta(+) (P < 0.01), CD8alpha(+) (P < 0.001), and NK(+) (P < 0.05) intestinal lymphocytes than Sham mice. There was a significant effect of exercise condition on total intestinal CD45(+) leukocytes (P < 0.01) and CD3alphabeta(+) (P < 0.05), CD8alpha(+) (P < 0.001), and CD4(+) (P < 0.05) intestinal lymphocytes, with fewer cells at 24 h postexercise compared with the other treatment conditions. There were no surgical x exercise interaction effects on the CD3 and CD8 phenotype numbers. Plasma corticosterone was virtually nil in ADX mice regardless of exercise condition but was significantly elevated in Sham mice immediately postexercise (P < 0.001). The data indicate that ADX does not prevent the loss of lymphocytes from the intestinal mucosa 24 h after strenuous exercise and GCs are not directly causal in the leukopenia of exercise.

Research paper thumbnail of Lymphocyte distribution in mouse submandibular lymph nodes in response to acute treadmill exercise

Canadian journal of …, Jan 1, 2003

Research paper thumbnail of Polyethylene glycol but not mifepristone prevents intestinal lymphocyte loss following treadmill exercise in mice

Acta Physiologica …, Jan 1, 2005

Research paper thumbnail of Long-duration freewheel running and submandibular lymphocyte response to forced exercise in older mice

Canadian journal of …, Jan 1, 2006

Abstract: Submandibular lymph nodes (SLN) are crucial for immune surveillance of the anterior ocu... more Abstract: Submandibular lymph nodes (SLN) are crucial for immune surveillance of the anterior ocular chamber and upper respiratory tract; little is known about how training and exercise affect SLN lymphocytes. The intent of this study was to describe the impact of long term ...