Platelets are dispensable for the ability of CD8+ T cells to accumulate, patrol, kill and reside in the liver

Effector and memory CD8+ T cells accumulate in large numbers in the liver where they play key roles in the control of liver pathogens including Plasmodium. It has also been proposed that liver may act as the main place for elimination of effector CD8+ T cells at the resolution of immune responses. Platelets and the integrin LFA-1 have been proposed to be critical for the accumulation of protective CD8+ T cells in the liver; conversely, asialo-glycoprotein (ASGP) expression on the surface of CD8+ T cells has been proposed to assist in elimination of effector T cells in the liver. Here we investigated the contributions of these interactions in the accumulation of CD8+ T cells activated in vitro or in vivo by immunization with Plasmodium parasites. Using Mpl-/- mice with constitutive thrombocytopaenia and antibody-mediated platelet depletion models we found that severe reduction in platelet concentration in circulation did not strongly influence the accumulation and protective function of CD8+ T cells in the liver in these models. Surprisingly, 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. We further found that enforced expression of ASGP on effector CD8+ T cells using ST3GalI knockout cells lead to their loss from the spleen. These data suggest that platelets play a marginal role in CD8+ T cell function in the liver. Furthermore, ASGP-expressing effector CD8+ T cells are retained in the liver but are lost from the spleen.