Role of macrophage D-region antigens and T-lymphocyte differentiation antigens in induction of gamma interferon.

Macrophage-T-lymphocyte cultures from patients with recent recurrent herpes labialis were stimulated to produce gamma interferon by either herpes simplex antigen or mitogens (PHA and Con A). The ability of monoclonal antibodies to HLA-DR and DC/DS, HSV glycoprotein antigens and T-lymphocyte surface antigens to inhibit interferon production and lymphocyte proliferation were studied. Anti-D region antibodies inhibited HSV antigen-induced but not mitogen-induced interferon and proliferation. The extent of inhibition varied mainly according to the determinants recognized by the antibodies and, to a lesser degree, between patients. Inhibition probably resulted from inhibition of antigen presentation, through antibody binding to macrophage D-region antigens. Interferon production was a more sensitive index of inhibition than lymphocyte proliferation. With one antibody (L227) a marked difference in inhibition in the two assays was noted, suggesting that lymphocytes producing gamma interferon may differ from the majority of the proliferating cells in their recognition of D-region determinants. Antibodies to the HSV glycoprotein antigens (gA/B, gC, gD, gE) did not produce consistent significant inhibition of interferon production and had no effect on proliferation. Anti-Leu 4 and -Leu 5 inhibited HSV antigen and mitogen induction of gamma interferon (and proliferation). Anti-Leu 2 and anti-Leu 3, mildly inhibitory alone, produced synergistic inhibition together. Hence, in human systems, the interaction between macrophages and T lymphocytes in producing gamma interferon appears to differ according to mode of induction. Macrophage D-region antigens are required for antigen induction probably via presentation whereas other factor(s), probably monokine secretion, are necessary for mitogen induction. Antibodies acting on the T-lymphocyte surface appear to affect a final common pathway of interferon induction, similar to their effects on proliferation and secretion of other lymphokines.