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Infection and Immunity, March 2004, p. 1358-1363, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1358-1363.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Effect of Neutralizing Transforming Growth Factor ß1 on the Immune Response against Mycobacterium tuberculosis in Guinea Pigs

Shannon Sedberry Allen,1* Lynne Cassone,2 Todd M. Lasco,1,{dagger} and David N. McMurray1

Department of Medical Microbiology & Immunology, Texas A&M University System Health Science Center,1 Texas A&M University College of Veterinary Medicine, College Station, Texas 778432

Received 30 June 2003/ Returned for modification 20 October 2003/ Accepted 10 December 2003

Transforming growth factor ß (TGF-ß) is a cytokine which has been shown to suppress the antimycobacterial immune responses of humans and experimental animals. In this study, the contributions of TGF-ß to cytokine production in vivo were investigated by using the established guinea pig model of tuberculous pleurisy. Mycobacterium bovis BCG-vaccinated guinea pigs were injected intrapleurally with heat-killed virulent Mycobacterium tuberculosis. Eight days following induction of an antigen-specific pleural effusion, guinea pigs were injected intrapleurally with anti-TGF-ß1 or isotype control antibody. The following day, pleural exudates were removed, and the fluid volume and characteristics of the infiltrating cells were determined. Pleural fluid was analyzed for total interferon (IFN) and tumor necrosis factor (TNF) protein levels by using appropriate bioassays. RNA from pleural effusion cells was examined to determine TGF-ß1, TNF-{alpha}, IFN-{gamma}, and interleukin-8 mRNA levels by using real-time PCR. Proliferative responses of pleural effusion lymphocytes were examined in response to concanavalin A and purified protein derivative (PPD) in vitro. Treatment with anti-TGF-ß1 resulted in decreased pleural fluid volume and decreased cell numbers in the pleural space along with an increased percentage of lymphocytes and a decreased percentage of neutrophils. The bioactive TNF protein levels in pleural fluid were increased in guinea pigs treated with anti-TGF-ß1, while the bioactive IFN protein concentrations were not altered. Expression of TGF-ß1 and TNF-{alpha} mRNA was significantly increased following TGF-ß1 neutralization. Finally, PPD-induced proliferative responses of pleural cells from anti-TGF-ß1-treated animals were significantly enhanced. Thus, TGF-ß1 may be involved in the resolution of this local, mycobacterial antigen-specific inflammatory response.


* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, 407 Reynolds Medical Building, College Station, TX 77843-1114. Phone: (979) 845-3679. Fax: (979) 845-3479. E-mail: sedberry{at}medicine.tamu.edu.

Editor: S. H. E. Kaufmann

{dagger} Present address: Department of Microbiology, Immunology & Pathology, Colorado State University, Ft. Collins, CO 80523-1682.


Infection and Immunity, March 2004, p. 1358-1363, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1358-1363.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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