Persistence and turnover of antigen-specific CD4 T cells during chronic tuberculosis infection in the mouse.
CD4 T cells are critical for resistance to Mycobacterium tuberculosis infection, but how effective T cell responses are maintained during chronic infection is not well understood. To address this question we examined the CD4 T cell response to a peptide from ESAT-6 during tuberculosis infection in the mouse. The ESAT-6(1-20)/IA(b)-specific CD4 T cell response in the lungs, mediastinal lymph nodes, and spleen reached maxima 3-4 wk postinfection, when the bacteria came under the control of the immune response. Once chronic infection was established, the relative frequencies of Ag-specific CD4 T cells were maintained at nearly constant levels for at least 160 days. ESAT-6(1-20)/IA(b)-specific CD4 T cells that responded in vitro expressed activation markers characteristic of chronically activated effector cells and used a limited Vbeta repertoire that was clonally stable in vivo for at least 12 wk. 5-Bromo-2-deoxyuridine incorporation studies indicated a relatively high rate of cell division among both total CD4 and ESAT-6(1-20)/IA(b)-specific CD4 T cells during acute infection, but the degree of 5-bromo-2-deoxyuridine incorporation by both the CD4 T cells and the Ag-specific cells declined at least 3-fold during chronic infection. The data indicate that the peripheral ESAT-6(1-20)/IA(b)-specific CD4 T cell response to M. tuberculosis is characterized during the acute phase of infection by a period of extensive proliferation, but once bacterial control is achieved, this is followed during chronic infection by an extended containment phase that is associated with a persistent response of activated, yet more slowly proliferating, T cells.
Winslow
Gary M
GM
Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12201, USA. gary.winslow@wadsworth.org
Roberts
Alan D
AD
Blackman
Marcia A
MA
Woodland
David L
DL
D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis / Q000276:immunology; D001426:Bacterial Proteins; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments