HIV type 1 envelope glycoprotein gp120 induces development of a T helper type 2 response to Cryptococcus neoformans

Objective: To analyse the contribution of HIV type 1 envelope glycoprotein gp120 to regulation of a T-cell response to Cryptococcus neoformans. Design: Monocytes treated with recombinant gp120 and exposed to C. neoformans were used as antigen presenting cells (APC) in coculture with autologous T lymphocytes. Methods: Costimulatory and major histocompatibility complex class II molecules were evaluated on APC by flow cytometry analysis. T-cell proliferation was determined as H-3 thymidine incorporation. Cytokine production was analysed by enzyme-linked immunosorbent assay. Results: gp120 had multiple effects on APC and the T-cell response including: (i) up-regulation of major histocompatibility complex class II antigens on the APC surface resulting from both redistribution of molecules from the intracellular pool and synthesis of new molecules; (ii) up-regulation of B7-2 molecules on the APC surface; (iii) altered T-cell proliferation; and (iv) promotion of interleukin-4 and inhibition of interferon-gamma synthesis and release. Conclusions: These data indicate that gp120 alters the normal T-cell response to C. neoformans, promoting a T-helper type 2 response. The altered T-cell response produced by gp120 may play an important role in the pathogenesis of cryptococcosis in the patient with AIDS. (C) 1999 Lippincott Williams & Wilkins.