Authors:
Zhuting Hu, Marcia A. Blackman, Kenneth M. Kaye, and Edward J. Usherwood
Summary:
CD4+ T cells are critical for the control of virus infections, T cell memory, and immune surveillance. We studied the differentiation and function of murine γ-herpesvirus 68 (MHV-68)–specific CD4+ T cells using gp150-specific TCR-transgenic mice. This allowed a more detailed study of the characteristics of the CD4+ T cell response than did previously available approaches for this virus. Most gp150-specific CD4+ T cells expressed T-bet and produced IFN-γ, indicating that MHV-68 infection triggered differentiation of CD4+ T cells largely into the Th1 subset, whereas some became follicular Th cells and Foxp3+ regulatory T cells. These CD4+ T cells were protective against MHV-68 infection in the absence of CD8+ T cells and B cells, and protection depended on IFN-γ secretion. Marked heterogeneity was observed in the CD4+ T cells, based on lymphocyte Ag 6C (Ly6C) expression. Ly6C expression positively correlated with IFN-γ, TNF-α, and granzyme B production; T-bet and KLRG1 expression; proliferation; and CD4+ T cell–mediated cytotoxicity. Ly6C expression inversely correlated with survival, CCR7 expression, and secondary expansion potential. Ly6C+ and Ly6C− gp150-specific CD4+ T cells were able to interconvert in a bidirectional manner upon secondary Ag exposure in vivo. These results indicate that Ly6C expression is closely associated with antiviral activity in effector CD4+ T cells but is inversely correlated with memory potential. Interconversion between Ly6C+ and Ly6C− cells may maintain a balance between the two Ag-specific CD4+ T cell populations during MHV-68 infection. These findings have significant implications for Ly6C as a surface marker to distinguish functionally distinct CD4+ T cells during persistent virus infection.
Source:
The Journal of Immunology; Vol.194, No. 6, 2746-2756 (03/15/15)