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Publication : Ectopic activation of Mycobacterium tuberculosis-specific CD4+ T cells in lungs of CCR7-/- mice.

First Author  Olmos S Year  2010
Journal  J Immunol Volume  184
Issue  2 Pages  895-901
PubMed ID  20007536 Mgi Jnum  J:159414
Mgi Id  MGI:4442561 Doi  10.4049/jimmunol.0901230
Citation  Olmos S, et al. (2010) Ectopic activation of Mycobacterium tuberculosis-specific CD4+ T cells in lungs of CCR7-/- mice. J Immunol 184(2):895-901
abstractText  Initiation of an adaptive cellular immune response depends on intimate interactions with APCs and naive T lymphocytes. We previously reported that activation of naive Mycobacterium tuberculosis-specific CD4+ T cells depends on dendritic cell (DC) transport of live bacteria from the lungs to the mediastinal lymph node (MDLN). Because the migratory paths of DCs are largely governed by the chemokine receptor CCR7, which is expressed on DCs upon maturation by proinflammatory stimuli, we examined the quantitative contribution of CCR7-dependent DC migration in the context of tuberculosis. We found that early trafficking of DCs from the lungs to the MDLN depended on CCR7-mediated signaling, but alternative mechanism(s) are used later in infection. Impaired migration of DCs in CCR7(-/-) mice resulted in delayed dissemination of bacteria to MDLN and spleen and in delayed kinetics of activation of adoptively transferred Ag85B-specific CD4+ T cells. Furthermore, in contrast to control mice, we found that naive Ag85B-specific CD4+ T cells are activated to proliferate in the lungs of CCR7(-/-) mice and, when infected with higher doses of bacteria, resistance to M. tuberculosis infection in CCR7(-/-) mice is compromised compared with wild-type mice.
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