Antigen-specific CD8+ T cells and the development of central memory during Mycobacterium tuberculosis infection.
Whether true memory T cells develop in the face of chronic infection such as tuberculosis remains controversial. To address this question, we studied CD8+ T cells specific for the Mycobacterium tuberculosis ESAT6-related Ags TB10.3 and TB10.4. The shared epitope TB10.3/10.4(20-28) is presented by H-2 K(d), and 20-30% of the CD8+ T cells in the lungs of chronically infected mice are specific for this Ag following respiratory infection with M. tuberculosis. These TB10.3/10.4(20-28)-specific CD8+ T cells produce IFN-gamma and TNF and express CD107 on their cell surface, which indicates their likely role as CTL in vivo. Nearly all of the Ag-specific CD8+ T cells in the lungs of chronically infected mice had a T effector cell phenotype based on their low expression of CD62L and CD45RB. In contrast, a population of TB10.3/10.4(20-28)-specific CD8+ T cells was identified in the lymphoid organs that express high levels of CD62L and CD45RB. Antibiotic treatment to resolve the infection led to a contraction of the Ag-specific CD8+ T cell population and was accompanied by an increase in the proportion of CD8+ T cells with a central memory phenotype. Finally, challenge of memory-immune mice with M. tuberculosis was accompanied by significant expansion of TB10.3/10.4(20-28)-specific CD8+ T cells, which suggests that these cells are in fact functional memory T cells.
Kamath
Arati
A
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA.
Woodworth
Joshua S M
JS
Behar
Samuel M
SM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008221:Lymphoid Tissue / Q000276:immunology / Q000382:microbiology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000942:Antigens, Bacterial; D052118:Lysosomal-Associated Membrane Protein 1; C501710:TB10.4 antigen, Mycobacterium tuberculosis; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens