DIFFERENTIAL REGULATION OF HUMAN, ANTIGEN-SPECIFIC TH1 AND TH2 RESPONSES BY THE B-7 HOMOLOGS, CD80 AND CD86

A selectivity of B7.1 (CD80) for promoting Th1 responses and B7.2 (CD8 6) for promoting Th2 responses in the murine system has recently been suggested. The present study explores this hypothesis, using human PBM Cs and antigen-specific Th1 and Th2 clones. Proliferative responses of peripheral blood mononuclear cells (PBMCs) from ragweed-allergic, tet anus toxoid-immunized individuals were downregulated by treatment with anti-CD86 in ragweed-and tetanus toxoid-driven cultures (% Inhibition = 55 +/- 4 and 61 +/- 12, respectively; P < 0.03 relative to untreate d cultures). Gene expression in PBMCs for interleukin (IL)-4, IL-5, an d interferon gamma (IFN gamma), assessed by reverse-transcriptase poly merase chain reaction, was also downregulated by treatment with anti-C D86 in both the ragweed-and tetanus toxoid-driven systems. Neither ind ependent efficacy nor synergy with anti-CD86 was apparent with anti-CD 80 treatment; two different anti-CD80 blocking antibodies yielded iden tical results. Conversely, antigen-specific Th1 and Th2 clones were in sensitive. to treatment with either anti-CD80, anti-CD86, or a combina tion of the two. Unaffected parameters included proliferative response (P < 0.14 and 0.33, respectively, for Th1 and Th2), proinflammatory c ytokine gene expression, and cytokine protein secretion into culture s upernatants (P < 0.44 and 0.16, respectively, for IL-4 and IFN gamma). We conclude that CD86 is the primary B7 signaling homologue in human PBMC responses, and that second signal pathways through the B7 homolog ues have no effect on phenotypically differentiated T helper cells in humans.