SHP-1 deficiency does not restore the CD8+ T cell response to an LCMV viral variant (P6079)

Abstract

Abstract 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.