T cell expansion is the limiting factor of virus control in mice with attenuated TCR signaling: Implications for human immunodeficiency
11.02.2015
Hillen KM, Gather R, Enders A, Pircher H, Aichele P, Fisch P, Blumenthal B, Schamel WW, Straub T, Goodnow CC, Ehl S.
J Immunol. 2015;194(6):2725-34
TCR signaling is critical for T cell development, activation, and effector functions. And thus, understanding the relevance of these processes in antiviral responses is of interest in BIOSS. To this end, we used a novel mouse strain with reduced expression of SLP76. Despite pronounced T cell activation defects ex vivo, these mice generated a normal proportion of antiviral effector T cells after infection with the ymphocytic choriomeningitis virus (LCMV). Their CD8+ T cells showed impaired cytokine production, whereas cytotoxicity as the crucial antiviral effector function for LCMV control was normal. The main limiting factor in the antiviral response of the SLP76low mice was impaired T cell proliferation and survival, leading to a 10-fold reduction of antiviral T cells at the peak of the immune response. This was still sufficient to control infection with the LCMV Armstrong strain, but the more rapidly replicating LCMV-WE induced T cell exhaustion and viral persistence. Thus, under conditions of impaired TCR signaling, reduced T cell expansion was the limiting factor in antiviral immunity.
