The impact of L-selectin/CD62L on the co-stimulation and migration of CD8+ T cells during virus infection

Abstract

The strategy of the adaptive immune system in eliminating viruses from infected tissues is the activation of CD8+ T cells with specific T cell receptor in the LN draining the site of virus entry and subsequent migration of these cells to the sites of the viral infection. L-selectin, a well characterized LN homing receptor, is variably expressed on virus peptide activated CD8+ T cells, regulated through two separate mechanisms of early ectodomain shedding and late gene silencing. The role of L-selectin in homing of activated CD8+ T cells to sites of virus infection is not studies in detail. Here we show that despite being primed normally in the draining LN, there were a hierarchy in homing ability of adoptively transferred CD8+ T cells expressing mutant L-selectin(which resist shedding and gene silencing upon T cell activation), wildtype Lselectin and deficient in L-selectin (Ko) to the site of virus infection. The Lselectin specific recruitment was confirmed by using antibody blockade strategy and short-term competitive homing experiments. Furthermore, Lselectin dependent homing of virus specific CD8+ T cells rather than hyperfunctional or hyperproliferative T cells conferred anti-viral immunity against two evolutionarily distinct viruses, vaccinia and influenza viruses which infect mucosal and visceral organs, respectively