title: Maintenance of peripheral T cell responses during Mycobacterium tuberculosis infection.
abstract: Fully functional T cells are necessary for the maintenance of protective immunity during chronic infections. However, activated T cells often undergo apoptosis or exhaustion upon chronic stimulation mediated by Ag or inflammation. T cell attrition can be compensated for by the production of thymus-derived T cells, although the new naive T cells must undergo T cell priming and differentiation under conditions different from those encountered during acute infection. We used a murine model of Mycobacterium tuberculosis infection to address how the activation and differentiation of new thymic emigrants is affected by chronic inflammation, as well as whether the newly developed effector T cells help to maintain peripheral T cell responses. Although new thymic emigrants contributed to the peripheral T cell response early during acute M. tuberculosis infection, the relative contribution of new effector T cells to the peripheral CD4 and CD8 T cell pools declined during chronic infection. The decline in new T cell recruitment was a consequence of quantitative and/or qualitative changes in Ag presentation, because during chronic infection both the priming and expansion of naive T cells were inefficient. Thus, although thymic tolerance is not a major factor that limits protective T cell responses, the chronic environment does not efficiently support naive T cell priming and accumulation during M. tuberculosis infection. These studies support our previous findings that long-term protective T cell responses can be maintained indefinitely in the periphery, but also suggest that the perturbation of homeostasis during chronic inflammatory responses may elicit immune pathology mediated by new T cells.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Reiley
authors.forename: Susan T
authors.initials: ST
authors.lastname: Wittmer
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Ryan
authors.forename: Sheri M
authors.initials: SM
authors.lastname: Eaton
authors.forename: Laura
authors.initials: L
authors.lastname: Haynes
authors.forename: Gary M
authors.initials: GM
authors.lastname: Winslow
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology