ABERRANT ANTIGEN PRESENTATION BY MACROPHAGES FROM TUMOR-BEARING MICE IS INVOLVED IN THE DOWN-REGULATION OF THEIR T-CELL RESPONSES

Splenic T cells from BALB/c mice bearing mammary adenocarcinomas initially demonstrate a primed response to tumor-associated Ags (TAA), which declines to presensitization levels within 4 wk after tumor implantation. Associated with this decline in responses to TAA is the expansion of a subpopulation of Mac-1(+) 2(+) splenic macrophages (M phi). These Mac-1(+) 2(+) cells present TAA inefficiently to normal T cells primed to TAA by footpad injection, as compared with the Ag presenting ability of M phi from normal mice. The addition of anti-I-E(d), but not anti-I-A(d), Ab blocked the ability of Ag-pulsed Mac-1(+) 2(+) cells to present TAA to primed T cells. The converse was observed with macrophages from normal mice. However, presentation of human gamma-globulin or OVA was restricted by I-A(d) molecules when APC from normal mice or tumor bearers were used, although less efficiently in the latter. Using cell depletion techniques, it was determined that the I-E(d)-restricted presentation preferentially expanded CD8(+) T cells, and not CD4(+) cells, as was the case for I-A(d)-restricted normal macrophages. These CD8(+) cells were poor effecters of cytotoxicity against tumor cells; instead they down-regulated the proliferative activity of T cells. Limiting dilution assays indicated that Mac-1(+) 2(+) macrophages preferentially present TAA to a low frequency inhibitory T cell population that expanded and inhibited further responses to TAA. Thus, alterations of Ag presentation in tumor bearers may help the tumor to subvert potential beneficial host responses and allow the progression of the neoplastic process.