Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis

James P., et al. 2007. JEM. 204, 2159-2169

Speaker: Yi Chun Chen (陳逸純)                                           Time: 13:00~14:00, Nov. 14, 2007

Commentator: Dr. Kao-Jean Huang (黃國珍博士)                Place: Room 601

Abstract:

Mycobacterium tuberculosis ( Mtb ) usually cause persistently infected and need to be treat by mechanisms that dampen immunity. T regulatory (T reg) cells can not only  preventing autoimmunity, but also suppress antimicrobial immune responses. In human tuberculosis, some studies have shown an increase in T reg numbers in the blood and at sites of infection during active disease, but the same appearance couldnt be find in the murine model because the lack of good markers to identify these cells. So the authors describe two approaches to circumvent these problems. First, they have used mice expressing GFP knocked into the locus encoding the forkhead transcription factor, Foxp3. Thus, T reg cells could be tracked by their expression of Foxp3-GFP fusion protein, and considerable quantities T reg cells has be found in perivascular/peribronchiolar regions and within lymphoid aggregates of granulomas. Second, they use a mixed bone marrow chimeric mice, and they were able to eliminate all cells capable of becoming Foxp3-expressing T reg cells in vivo using a depleting anti-Thy1.1 antibody. Thus, they depleted T reg cells by administration of anti-Thy1.1 before aerosol infection with Mtb., and observed an advancement colony-forming units in the lungs. Besides, they also found that T reg cells proliferated in the pulmonary lymph nodes (pLNs) during tuberculosis, and Foxp3-expressing T reg cells in tuberculosis did not produce effector cytokines or IL-10. T reg cells increase inducible costimulatory molecule (ICOS), and change their cell surface phenotype. The accumulation of T reg cell is simillar to effector T cells. These results demonstrate that T reg cells have the capacity to suppress immune responses that control Mtb, especially in the lung.

References:

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2.      Fontenot, J.D., J.P. Rasmussen, L.M. Williams, J.L. Dooley, A.G. Farr, and A.Y. Rudensky. 2005. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity. 22:329–341.