Effect of Attenuation of Treg during BCG Immunization on Anti-Mycobacterial Th1 Responses and Protection against Mycobacterium tuberculosis
| Autor: | Claude Leclerc, Barbara Jaron, Eddie Maranghi, Laleh Majlessi |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
CD4-Positive T-Lymphocytes
T-Lymphocytes Immunology lcsh:Medicine chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Models Biological T-Lymphocytes Regulatory Mycobacterium Mycobacterium tuberculosis Infectious Diseases/Bacterial Infections 03 medical and health sciences Mice 0302 clinical medicine Immune system Antigen Immunology/Immunity to Infections Cytotoxic T cell Animals lcsh:Science Lung 030304 developmental biology 0303 health sciences Mice Inbred BALB C Multidisciplinary biology Effector Infectious Diseases/Respiratory Infections lcsh:R Interleukin-2 Receptor alpha Subunit hemic and immune systems Th1 Cells biology.organism_classification Virology 3. Good health Microbiology/Immunity to Infections BCG Vaccine Female lcsh:Q Th1 response BCG vaccine 030215 immunology Research Article |
| Zdroj: | PLoS ONE, Vol 3, Iss 7, p e2833 (2008) PLoS ONE |
| Popis: | 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-Guérin) 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-gamma 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 compared to the control mice. CONCLUSIONS: Our results provide the first demonstration that attenuation of Treg subset concomitant to BCG vaccination has a positive, yet limited, impact on the protective capacity of this vaccine against infection with M. tuberculosis. Thus, for rational design of improved BCG, it should be considered that, although the action of Treg does not represent the major cause of the limited efficiency of BCG, the impact of this cell population on the subsequent control of M. tuberculosis growth is significant and measurable. |
| Databáze: | OpenAIRE |
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