effect of attenuation of treg during bcg immunization on anti-mycobacterial th1 responses and protection against mycobacterium tuberculosis效应的衰减treg在bcg免疫anti-mycobacterial th1反应和预防结核分枝杆菌.pdfVIP

Effect of Attenuation of Treg during BCG Immunization on Anti-Mycobacterial Th1 Responses and Protection against Mycobacterium tuberculosis 1,3 2 1,3 1,3 Barbara Jaron , Eddie Maranghi , Claude Leclerc , Laleh Majlessi * ´ ´ ´ 1 Unite de Regulation Immunitaire et Vaccinologie, Institut Pasteur, Paris, France, 2 Animalerie Centrale, Institut Pasteur, Paris, France, 3 Institut National de la Sante et de ´ la Recherche Medicale U883, Paris, France Abstract Background: The functional equilibrium between natural regulatory T cells (Treg) and effector T cells can affect the issue of numerous infections. In unvaccinated mice, the influence of Treg in the control of primary infection with mycobacteria remains controversial. Methodology: Here, we evaluated the role of Treg during prophylactic vaccination with Mycobacterium bovis BCG (Bacillus ´ Calmette-Guerin) on the induction of T cell responses and on the protective effect against subsequent M. tuberculosis challenge in mice. Principal Findings: We demonstrated that, subsequent to BCG injection, Treg were recruited to the draining lymph nodes and negatively control anti-mycobacterial CD4+ — but not CD8+ — T-cell responses. Treatment of BCG-immunized mice with an anti-CD25 mAb (PC61) induced an increase IFN-c response against both subdominant and immunodominant regions of the protective immunogen TB10.4. In Treg-attenuated, BCG-immunized mice, which were then infected with M. tuberculosis, the lung mycobacterial load was significantly, albeit moderately, reduced