A MECHANISM FOR SELECTIVE RECRUITMENT OF CD8 T-CELLS INTO B7-1-TRANSFECTED PLASMACYTOMA - ROLE OF MACROPHAGE-INFLAMMATORY PROTEIN 1-ALPHA

An important aspect of immunity is the recruitment and accumulation of lymphocytes into target tissues where Ags are localized, Because the TCR recognizes antigenic peptides presented by MHC molecules, the subs et of T cells that exert effector function is determined by the class of MHC molecules expressed on a given tissue, We and others have demon strated that CD8 Upsilon cells are preferentially recruited into B7-1- transfected class II-negative plasmacytoma J558, and the virus-infecte d central nervous system. However, the mechanism for such specificity has not been addressed, Here we analyzed the mechanism for selective r ecruitment of CD8 T cells into B7-1-transfected plasmacytoma J558, We show that sustained accumulation of CD8 T cells in vivo requires local expression of B7-1, In addition, we have observed a striking correlat ion between expression of macrophage-inflammatory protein 1 alpha (MIP 1 alpha) and selective accumulation of CD8 T cells in tile tumors, The selective recruitment of CD8 T cells is blocked by in vivo administra tion of neutralizing anti-MIP1 alpha antisera. Moreover, gene-transfer studies reveal that locally produced MIP1 alpha is sufficient to indu ce selective recruitment of CD8 T cells, Taken together, our study rev eals that costimulation by B7 leads to sustained local production of M IP1 alpha, which selectively recruits CD8 T cells into tumors. These r esults have important implications for T cell recruitment in vivo and for tumor immunotherapy.