Viruses employ various mechanisms to evade recognition by host immune effectors and establish persistence in the host. We have previously shown that CD8+ T cells responding to a viral variant of lymphocytic choriomeningitis virus (LCMV) have high SHP-1 activity. Src homology region 2 domain-containing phosphatase-1 (SHP-1) is a non-receptor phosphatase found in hematopoietic cells and is thought to play a primarily negative regulatory role in many signaling pathways. SHP-1 exerts important negative regulation on proximal TCR signaling by blocking early T cell activation. Because of its role in dampening TCR signaling, we hypothesized that removal of SHP-1 in T cells would restore the response to the viral variant. Using CD4 Cre Fl SHP-1 mice, we evaluated the generation, activation and functionality of CD8+ T cells generated in response to the viral escape mutant. Loss of SHP-1 did not greatly affect response of the P14 TCR Tg cells line assessed in vitro. In vivo analysis of the response to the viral escape mutant did not demonstrate increased T cell numbers or functionality (IFNg secretion) in response to the viral escape mutant or the control chronic viral LCMV infection. Polyclonal T cell responses to the viral challenges were unaffected by SHP-1 deficient. These observations suggest that removal of a negative regulator may not have the expected therapeutic benefit of an enhanced T cell response.
- Copyright © 2013 by The American Association of Immunologists, Inc.