HIV-INDUCED IL-6 IL-10 DYSREGULATION OF CD4 CELLS IS ASSOCIATED WITH DEFECTIVE B-CELL HELP AND AUTOANTIBODY FORMATION AGAINST CD4 CELLS/

To analyse CD4 cell cytokine secretion and helper/suppressor function at a clonal level we established 446 CD4(+) T cell clones (TCC) in fou r healthy controls, three HIV-haemophilia patients, four CDC II,III an d four CDC IV patients. Spontaneous TCC secretion of Th1 cytokines (IL -2, interferon-gamma (IFN-gamma)) and Th2 cytokines (IL-4, IL-6, IL-10 ) was determined by ELISA. TCC helper and suppressor functions were te sted in a pokeweed mitogen (PWM)-stimulated allogeneic co-culture syst em using a reverse haemolytic plaque assay for assessment of B cell re sponses. There was a significant association of TCC surface marker exp ression (Leu-8, CD45RA) with TCC IL-6 secretion in healthy controls (P < 0.01), HIV- patients (P less than or equal to 0.001) and CDC II,III patients (P less than or equal to 0.01) but not in CDC TV patients. L ikewise, TCC expression of Leu-8 and CD45RA was significantly associat ed with TCC suppressor function in healthy controls (P less than or eq ual to 0.0005) but not in HIV-infected patients. A reduced TCC helper frequency (less than or equal to 10% of TCC) and an enhanced TCC suppr essor frequency (> 80% of TCC) were detected only in those HIV-infecte d patients who showed an excessively increased TCC IL-6 secretion (> 7 0% of TCC) together with a significantly diminished TCC IL-10 secretio n (less than or equal to 10% of TCC). CD4 cell autoantibodies also wer e found only in patients with this type of cytokine dysregulation. The se data indicate that CD4 cell surface markers lose their functional r elevance in HIV-infected patients. HIV-induced IL-6/IL-10 dysregulatio n of CD4(+) T cells, i.e. the up-regulation of spontaneous IL-6 and do wn regulation of spontaneous IL-10 secretion, appears to be involved i n inducing CD4 helper defects and may promote autoantibody formation a gainst CD4 cells.