Activation of human CD8+ alpha beta TCR+ cells by Mycobacterium tuberculosis via an alternate class I MHC antigen-processing pathway.
Human immune responses to M. tuberculosis are characterized by activation of multiple T cell subsets including CD4+, CD8+, and gammadelta T cells, and the role of CD8+ alphabeta TCR+ T cells in this response is poorly understood. Stimulation of T cells from healthy tuberculin skin test-positive persons with live M. tuberculosis-H37Ra or soluble M. tuberculosis Ags readily up-regulated IL-2Ralpha (CD25) expression on CD8+ T cells. Purified resting and activated CD8+ T cells produced IFN-gamma and proliferated to both M. tuberculosis bacilli and soluble mycobacterial Ags with monocytes as APC. Precursor frequency of mycobacterial Ag-specific CD8+ T cells by IFN-gamma enzyme-linked immunospot was 5-10-fold lower than the precursor frequency of CD4+ T cells, and IFN-gamma secretion by CD8+ T cells was 50-100-fold lower. CD8+ T cells secreted approximately 10-fold less IFN-gamma per cell than CD4+ T cells in response to mycobacterial Ags. CD8+ T cell responses to M. tuberculosis bacilli were blocked by anti-MHC class I antibody and required Ag processing. Processing of M. tuberculosis bacilli by monocytes for presentation to MHC class I-restricted CD8+ T cells was insensitive to brefeldin A treatment, which blocks the conventional MHC class I Ag-processing pathway. These results represent the first demonstration that human cells can process pathogen Ags via an alternate Ag-processing pathway for MHC class I and suggest a mechanism for participation of IFN-gamma-secreting CD8+ T cells in the human immune responses to M. tuberculosis.
Canaday
D H
DH
Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland, OH 44106, USA. dxc44@cwru.edu
Ziebold
C
C
Noss
E H
EH
Chervenak
K A
KA
Harding
C V
CV
Boom
W H
WH
D017951:Antigen Presentation / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012995:Solubility; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014373:Tuberculin / Q000097:blood / Q000494:pharmacology
D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014373:Tuberculin; D007371:Interferon-gamma