[PDF][PDF] Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection

U Dittmer, H He, RJ Messer, S Schimmer, ARM Olbrich… - Immunity, 2004 - cell.com
U Dittmer, H He, RJ Messer, S Schimmer, ARM Olbrich, C Ohlen, PD Greenberg
Immunity, 2004cell.com
The establishment of viral persistence generally requires evasion of the host CD8+ T cell
response. Here we describe a form of evasion wherein the CD8+ T cells are fully capable of
recognizing their cognate antigen but their effector functions are suppressed by regulatory T
cells. Virus-specific CD8+ T cells adoptively transferred into mice persistently infected with
Friend virus proliferated and appeared activated, but failed to produce IFNγ or reduce virus
loads. Cotransfer experiments revealed that a subpopulation of CD4+ T cells from …
The establishment of viral persistence generally requires evasion of the host CD8+ T cell response. Here we describe a form of evasion wherein the CD8+ T cells are fully capable of recognizing their cognate antigen but their effector functions are suppressed by regulatory T cells. Virus-specific CD8+ T cells adoptively transferred into mice persistently infected with Friend virus proliferated and appeared activated, but failed to produce IFNγ or reduce virus loads. Cotransfer experiments revealed that a subpopulation of CD4+ T cells from persistently infected mice suppressed IFNγ production by the CD8+ T cells. Treatment of persistently infected mice with anti-GITR antibody to ameliorate suppression by regulatory T cells significantly improved IFNγ production by transferred CD8+ T cells and allowed a significant reduction in viral loads. The results indicate that CD4+ regulatory T cells contribute to viral persistence and demonstrate an immunotherapy for treating chronic retroviral infections.
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