Interleukin-12 counterbalances the deleterious effect of human immunodeficiency virus type 1 envelope glycoprotein gp120 on the immune response to Cryptococcus neoformans

The mechanism involved in the envelope glycoprotein gp120-induced Th2 respo nse to Cryptococcus neoformans was investigated. Peripheral blood mononucle ar cells (PBMC) from healthy donors were treated with human immunodeficienc y virus gp120 and an encapsulated or acapsular strain of C. neoformans in t he presence or absence of glucuronoxylomannan, the major capsular polysacch aride. gp120 inhibited early and late production of interleukin (IL)-12 by PBMC. This reduction paralleled IL-10 induction and inhibited translocation of CD40 to the surface of monocytes. Flow cytometric analysis revealed tha t gp120 downregulated the expression of IL-12 receptor beta2 subunit on T c ells responding to C. neoformans. Because the IL-12/IL-12 receptor beta2 su bunit pathway is critical for the Th1 differentiation process, underexpress ion demonstrates that gp120 contributes to Th2 bias. Exogenous IL-12 added simultaneously with gp120 up-regulated interferon-gamma secretion and limit ed IL-4 production. These results suggest that gp120 limits the Th1 respons e to C. neoformans and that exogenous IL-12 could offset this effect.