Abstract
Liver-resident CD8(+) T cells can play critical roles in the control of pathogens, including Plasmodium and hepatitis B virus. Paradoxically, it has also been proposed that the liver may act as the main place for the elimination of CD8(+) T cells at the resolution of immune responses. We hypothesized that different adhesion processes may drive residence versus elimination of T cells in the liver. Specifically, we investigated whether the expression of asialo-glycoproteins (ASGPs) drives the localization and elimination of effector CD8(+) T cells in the liver, while interactions with platelets facilitate liver residence and protective function. Using murine CD8(+) T cells activated in vitro, or in vivo by immunization with Plasmodium berghei sporozoites, we found that, unexpectedly, inhibition of ASGP receptors did not inhibit the accumulation of effector cells in the liver, but instead prevented these cells from accumulating in the spleen. In addition, enforced expression of ASGP on effector CD8(+) T cells using St3GalI-deficient cells lead to their loss from the spleen. We also found, using different mouse models of thrombocytopenia, that severe reduction in platelet concentration in circulation did not strongly influence the residence and protective function of CD8(+) T cells in the liver. These data suggest that platelets play a marginal role in CD8(+) T cell function in the liver. Furthermore, ASGP-expressing effector CD8(+) T cells accumulate in the spleen, not the liver, prior to their destruction.