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Mechanisms of control of acute Friend virus infection by CD4+ helper T cells and their functional impairment by regulatory T cells

¹ University Clinics Essen, University Duisburg-Essen;
² Comparative Genomics Centre, James Crook University;
³ MRC National Institute for Medical Research

⁴ E-mail: ulf.dittmer{at}uni-essen.de

The role of Cytotoxic CD8+ T cells (CD8+ CTLs) is well defined in retroviral immunity but the role of CD4+ T helper (Th) cells is poorly understood. The Friend retrovirus (FV) murine infection model is a good model to study immune responses in retroviral infections and hence was used to characterize the role of Th cells during acute infection. In vivo depletion of Th cells in acutely infected mice demonstrated that Th cells were vital in controlling viral spread and onset of erythroleukemia and for the maintenance of FV-specific CD8+ T-cell and neutralizing antibody responses. Kinetic analysis of FV-specific Th cell responses using class-II tetramers showed that the magnitude of the Th cell response correlated with the level of resistance to FV-induced leukemia in different mouse strains. FV-specific CD4+ T-cell receptor (TCR) beta transgenic (CD4+ TCR beta-tg) T-cells were adoptively transferred into mice infected for different time periods (1 wpi, 2 wpi, 3 wpi) to investigate the direct anti-viral effect of CD4+ T cells in FV infection. Results indicated that FV-specific CD4+ TCR beta-tg T cells were functionally active until 2 wpi, including their ability to produce IFN-g and reduce viral loads. However, the donor cells lost their anti-viral activity starting from 3 wpi. Interestingly, in vivo depletion of regulatory T-cells (Tregs) at this time point restored IFN-g production by transferred CD4+ T cells. Current study reveals that Th cells were critical for recovery from acute Friend retroviral infection but were functionally impaired during the late phase of acute infection due to induced Tregs.

Received 17 August 2009; accepted 13 October 2009.