Transforming growth factor beta 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 beta (TGF-beta) in cellular immune responses of 20 patients with chronic brucellosis. Circulating TGF-beta1 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-beta1 production was demonstrated in patients peripheral blood mononuclear cells (PBMC)-stimulated with Brucella cell extract (BCE) antigen. The increased production of TGF-beta1 protein was dually associated with enhanced expression of TGF-beta mRNA in patients PBMC and diminished lymphoproliferative responses to BCE. A causal relationship between increased TGF-beta1 production and depressed lymphoproliferative responses was demonstrated by treatment of proliferating PBMC with a neutralizing antibody to TGF-beta1 where the lymphocytes function has been restored. These results suggest that the increased activity of TGF-beta1 may underlie the depressed function of T cell responses with consequent prolongation of disease course in patients with chronic brucellosis.
Elfaki
Mohamed G
MG
Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Takhassusi Road, PO Box 3354, MBC 03, Riyadh 11211, Saudi Arabia. elfaki@kfshrc.edu.sa
Al-Hokail
Abdullah A
AA
D000328:Adult; D017347:Brucella melitensis / Q000276:immunology; D002006:Brucellosis / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
D053773:Transforming Growth Factor beta1