A mechanism for selective recruitment of CD8 T cells into B7-1-transfected plasmacytoma: role of macrophage-inflammatory protein 1alpha.
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 subset of T cells that exert effector function is determined by the class of MHC molecules expressed on a given tissue. We and others have demonstrated that CD8 T cells are preferentially recruited into B7-1-transfected class II-negative plasmacytoma J558, and the virus-infected central nervous system. However, the mechanism for such specificity has not been addressed. Here we analyzed the mechanism for selective recruitment 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 correlation between expression of macrophage-inflammatory protein 1alpha (MIP1alpha) and selective accumulation of CD8 T cells in the tumors. The selective recruitment of CD8 T cells is blocked by in vivo administration of neutralizing anti-MIP1alpha antisera. Moreover, gene-transfer studies reveal that locally produced MIP1alpha is sufficient to induce selective recruitment of CD8 T cells. Taken together, our study reveals that costimulation by B7 leads to sustained local production of MIP1alpha, which selectively recruits CD8 T cells into tumors. These results have important implications for T cell recruitment in vivo and for tumor immunotherapy.
Maric
M
M
Department of Pathology, New York University Medical Center, NY 10016, USA.
Chen
L
L
Sherry
B
B
Liu
Y
Y
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054407:Chemokine CCL4; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000276:immunology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D010954:Plasmacytoma / Q000276:immunology* / Q000473:pathology; D014162:Transfection
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins