Transforming growth factor β production correlates with depressed lymphocytes function in humans with chronic brucellosis

In chronic brucellosis due to Brucella melitensis, cell-mediated responses were transiently depressed in comparison to antibody responses. To elucidate the mechanism of immunosuppression, we examined the role of transforming growth factor β (TGF-β) in cellular immune responses of 20 patients with chronic brucellosis. Circulating TGF-β1 level was markedly elevated is sera of patients with confirmed brucellosis as compared with those from Brucella-negative healthy control subjects. In contrast, a 2-fold increase of TGF-β1 production was demonstrated in patients peripheral blood mononuclear cells (PBMC)-stimulated with Brucella cell extract (BCE) antigen. The increased production of TGF-β1 protein was dually associated with enhanced expression of TGF-β mRNA in patients PBMC and diminished lymphoproliferative responses to BCE. A causal relationship between increased TGF-β1 production and depressed lymphoproliferative responses was demonstrated by treatment of proliferating PBMC with a neutralizing antibody to TGF-β1 where the lymphocytes function has been restored. These results suggest that the increased activity of TGF-β1 may underlie the depressed function of T cell responses with consequent prolongation of disease course in patients with chronic brucellosis.