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 initi ally demonstrate a primed response to tumor-associated Ags (TAA), whic h declines to presensitization levels within 4 wk after tumor implanta tion. Associated with this decline in responses to TAA is the expansio n of a subpopulation of Mac-1(+) 2(+) splenic macrophages (M phi). The se Mac-1(+) 2(+) cells present TAA inefficiently to normal T cells pri med to TAA by footpad injection, as compared with the Ag presenting ab ility 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 t o present TAA to primed T cells. The converse was observed with macrop hages 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. Usi ng cell depletion techniques, it was determined that the I-E(d)-restri cted presentation preferentially expanded CD8(+) T cells, and not CD4( +) cells, as was the case for I-A(d)-restricted normal macrophages. Th ese CD8(+) cells were poor effecters of cytotoxicity against tumor cel ls; instead they down-regulated the proliferative activity of T cells. Limiting dilution assays indicated that Mac-1(+) 2(+) macrophages pre ferentially present TAA to a low frequency inhibitory T cell populatio n that expanded and inhibited further responses to TAA. Thus, alterati ons of Ag presentation in tumor bearers may help the tumor to subvert potential beneficial host responses and allow the progression of the n eoplastic process.