TY - JOUR
T1 - Early virus-associated bystander events affect the fitness of the CD8 T cell response to persistent virus infection
AU - Andrews, Nicolas P.
AU - Pack, Christopher D.
AU - Vezys, Vaiva
AU - Barber, Glen N.
AU - Lukacher, Aron E.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - Chronic Ag exposure during persistent viral infection erodes virus-specific CD8 T cell numbers and effector function, with a concomitant loss of pathogen control. Less clear are the respective contributions of Ag-specific and Ag-nonspecific (bystander) events on the quantity, quality, and maintenance off antiviral CD8 T cells responding to persistent virus infection. In this study, we show that low-dose inoculation with mouse polyomavirus (PyV) elicits a delayed, but numerically equivalent, antiviral CD8 T cell response compared with high-dose inoculation. Low-dose infection generated virus-specific CDS T cells endowed with multicytokine functionality and a superior per cell capacity to produce IFN-γ. PyV-specific CDS T cells primed by low-dose inoculation also expressed higher levels of IL-7Rα and bcl-2 and possessed enhanced Ag-independent survival. Importantly, the quantity and quality of the antiviral CD8 T cell response elicited by dendritic cell-mediated immunization were mitigated by infection with a mutant PyV lacking the dominant CD8 T cell viral epitope. These findings suggest that the fitness of the CDS T cell response to persistent virus infection is programmed in large part by early virus-associated Ag-nonspecific factors, and imply that limiting bystander inflammation at the time of inoculation, independent of Ag load, may optimize adaptive immunity to persistent viral infection.
AB - Chronic Ag exposure during persistent viral infection erodes virus-specific CD8 T cell numbers and effector function, with a concomitant loss of pathogen control. Less clear are the respective contributions of Ag-specific and Ag-nonspecific (bystander) events on the quantity, quality, and maintenance off antiviral CD8 T cells responding to persistent virus infection. In this study, we show that low-dose inoculation with mouse polyomavirus (PyV) elicits a delayed, but numerically equivalent, antiviral CD8 T cell response compared with high-dose inoculation. Low-dose infection generated virus-specific CDS T cells endowed with multicytokine functionality and a superior per cell capacity to produce IFN-γ. PyV-specific CDS T cells primed by low-dose inoculation also expressed higher levels of IL-7Rα and bcl-2 and possessed enhanced Ag-independent survival. Importantly, the quantity and quality of the antiviral CD8 T cell response elicited by dendritic cell-mediated immunization were mitigated by infection with a mutant PyV lacking the dominant CD8 T cell viral epitope. These findings suggest that the fitness of the CDS T cell response to persistent virus infection is programmed in large part by early virus-associated Ag-nonspecific factors, and imply that limiting bystander inflammation at the time of inoculation, independent of Ag load, may optimize adaptive immunity to persistent viral infection.
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U2 - 10.4049/jimmunol.178.11.7267
DO - 10.4049/jimmunol.178.11.7267
M3 - Article
C2 - 17513776
AN - SCOPUS:34249806015
SN - 0022-1767
VL - 178
SP - 7267
EP - 7275
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -