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

Mohamed G Elfaki1, Abdullah A Al-Hokail

  • 1Department 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

Microbes and Infection
|August 12, 2009
PubMed

Insights

Transforming growth factor beta (TGF-beta) elevates in chronic brucellosis, suppressing T cell responses. Neutralizing TGF-beta restored immune function, suggesting a therapeutic target for this persistent infection.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Chronic brucellosis involves immune dysregulation, with impaired cell-mediated immunity.
  • The role of specific immunosuppressive factors in *Brucella melitensis* infection requires elucidation.

Purpose of the Study:

  • To investigate the involvement of transforming growth factor beta (TGF-beta) in the immunosuppression observed in chronic brucellosis.
  • To determine the relationship between TGF-beta levels and T cell dysfunction in patients with *Brucella melitensis* infection.

Main Methods:

  • Quantification of circulating TGF-beta1 levels in patients and healthy controls.
  • Measurement of TGF-beta1 production by peripheral blood mononuclear cells (PBMC) stimulated with *Brucella* cell extract (BCE).
  • Assessment of TGF-beta mRNA expression and lymphoproliferative responses in patient PBMC.
  • In vitro experiments using neutralizing antibodies to TGF-beta to restore lymphocyte function.

Main Results:

  • Markedly elevated serum TGF-beta1 levels were found in patients with chronic brucellosis compared to controls.
  • Stimulation with BCE antigen induced a 2-fold increase in TGF-beta1 production and mRNA expression in patient PBMC.
  • Increased TGF-beta1 production correlated with diminished lymphoproliferative responses to BCE.
  • Neutralization of TGF-beta1 restored the function of proliferating lymphocytes.

Conclusions:

  • Elevated TGF-beta1 activity contributes to the depressed T cell function in chronic brucellosis.
  • This TGF-beta1-mediated immunosuppression may lead to a prolonged disease course.
  • Targeting TGF-beta1 presents a potential therapeutic strategy for managing chronic brucellosis.