Delayed protection by ESAT-6-specific effector CD4+ T cells after airborne M. tuberculosis infection Journal Article
| Authors: | Gallegos, A. M.; Pamer, E. G.; Glickman, M. S. |
| Article Title: | Delayed protection by ESAT-6-specific effector CD4+ T cells after airborne M. tuberculosis infection |
| Abstract: | Mycobacterium tuberculosis infection induces complex CD4 T cell responses that include T helper type 1 (Th1) cells and regulatory T cells. Although Th1 cells control infection, they are unable to fully eliminate M. tuberculosis, suggesting that Th1-mediated immunity is restrained from its full sterilizing potential. Investigation into T cell-mediated defense is hindered by difficulties in expanding M. tuberculosis-specific T cells. To circumvent this problem, we cloned CD4+ T cells from M. tuberculosis-infected B6 mice and generated transgenic mice expressing a T cell receptor specific for the immunodominant antigen early secreted antigenic target 6 (ESAT-6). Adoptively transferred naive ESAT-6-specific CD4+ T cells are activated in pulmonary lymph nodes between 7 and 10 d after aerosol infection and undergo robust expansion before trafficking to the lung. Adoptive transfer of activated ESAT-6-specific Th1 cells into naive recipients before aerosol M. tuberculosis infection dramatically enhances resistance, resulting in 100-fold fewer bacteria in infected lungs. However, despite large numbers of Th1 cells in the lungs of mice at the time of M. tuberculosis challenge, protection was not manifested until after 7 d following infection. Our results demonstrate that pathogen-specific Th1 cells can provide protection against inhaled M. tuberculosis, but only after the first week of infection. © 2008 Gallegos et al. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; animals; mice; animal experiment; animal model; time factors; mice, transgenic; lymphocyte differentiation; mycobacterium tuberculosis; bacterial proteins; receptors, antigen, t-cell; lymph node; cd4+ t lymphocyte; cd4-positive t-lymphocytes; adoptive transfer; effector cell; th1 cell; cell protection; tuberculosis; airborne infection; th1 cells; antigens, bacterial; early secretory antigenic target 6 |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 205 |
| Issue: | 10 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2008-09-29 |
| Start Page: | 2359 |
| End Page: | 2368 |
| Language: | English |
| DOI: | 10.1084/jem.20080353 |
| PUBMED: | 18779346 |
| PROVIDER: | scopus |
| PMCID: | PMC2556792 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 34" - "Export Date: 17 November 2011" - "CODEN: JEMEA" - "Source: Scopus" |
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