2 and Table 3). and CDC II,III patients ( 001) but not in CDC IV patients. Likewise, TCC expression of Leu-8 and CD45RA was significantly associated with TCC suppressor function in healthy controls ( 00005) but not in HIV-infected patients. A reduced TCC helper frequency ( 10% of TCC) and an enhanced TCC suppressor frequency ( 80% of TCC) Cefadroxil were detected only in those HIV-infected patients who showed an excessively increased TCC IL-6 secretion ( 70% of TCC) together with a significantly diminished TCC IL-10 secretion ( 10% of TCC). CD4 cell autoantibodies also were found only in patients with this type of cytokine dysregulation. These data indicate that CD4 cell surface markers lose their functional relevance in HIV-infected patients. HIV-induced IL-6/IL-10 dysregulation of CD4+ T cells, i.e. the up-regulation of spontaneous IL-6 and down-regulation of spontaneous IL-10 secretion, appears to be involved in inducing CD4 helper defects and may promote autoantibody formation against CD4 cells. [5] described an impaired proliferative capacity and abnormal cytokine profiles both in naive and memory CD4 cells of HIV-infected patients. HIV-induced expansion of the CD7? CD4 subset may explain an increase in the Th0/Th2 type of cytokine secretion [6]. However, even the data concerning a shift in CD4 cell cytokine secretion during the course of HIV infectionas suggested by the Th1/Th2 hypothesis [7C11]are contradictory. Romagnani [12, 13] and Graziosi [14] did not confirm a Th1/Th2 switch during disease progression when cytokine mRNA expression in lymphoid tissue and cytokine secretion of stimulated mononuclear cells, CD4+ T cells or T cell clones (TCC) were tested. We showed previously that CD4 helper defects in HIV-infected patients were significantly associated with autoantibody formation against CD4+ T cells Cefadroxil [15C18]. A role of IL-6 in the defective B cell help, but also in polyclonal B cell stimulation, impaired mitogen-stimulated B cell responses and autoantibody formation of HIV-infected patients, has been suggested [19C22]. However, we showed subsequently that application of rIL-2, rIL-4 and rIL-6 did not restore B cell responses in HIV-infected patients [23]. Thus, the impaired IL-2, IL-4 and IL-6 responses observed upon stimulation do not appear to be the cause of defective HIV-induced B cell responses. The pleiotropic cytokine IL-10 might play an essential role in B cell dysregulation of HIV-infected patients, as IL-10 not only suppresses cell-mediated immunity [24C26] but also acts as a potent growth and differentiation factor for activated B lymphocytes [27, 28]. Increased serum IL-10 levels, increased IL-10 expression in lymph nodes, Cefadroxil increased mitogen-stimulated IL-10 secretion and also increased IL-10 mRNA levels in CD4+ T cells were found in HIV-infected patients Cefadroxil [29C32]. IL-10 may even play a role in autoimmunity, as suggested by the finding that immunoglobulin production by B cells of systemic lupus erythematosus (SLE) patients is largely IL-10-dependent [33]. In the present study we investigate whether HIV-induced helper/suppressor dysfunctions of CD4+ TCC are due to shifts in CD4 cell subsets or to an intrinsic abnormality of individual CD4 cells. We analyse whether spontaneous Th1 (IL-2, inferferon-gamma (IFN-)) or Th2 (IL-4, IL-6, IL-10) cytokine secretion is accompanied by TCC helper defects/suppressor activity and autoantibody formation against CD4 LIT cells. PATIENTS AND METHODS Haemophilia patients Blood samples of 11 patients with haemophilia A and four healthy controls were used to establish TCC. Three patients were HIV?, four CDC stage II or III, and four CDC stage IV. Patient 10 (CDC II,III) was tested twice within 1 year. Aside from intestinal candidiasis in patients 12 and 13, no other coinfections were present. One CDC II,III patient (patient 11) and one CDC Cefadroxil IV patient (patient 13) were moderately affected by haemophilia A (factor VIII activity 16% and 10%, respectively), the other.