Characterization of effector functions of human peptide-specific CD4+ T-cell clones for an intracellular pathogen.
CD4+ T cells are believed to play a dominant role in human defenses against Mycobacterium tuberculosis through production of interferon (IFN)-gamma, cytolytic T-cell (CTL) activity, and inhibition of intracellular mycobacterial growth. Most functional studies of CD4+ cells have used bulk T-cells that recognize crude mycobacterial antigens, and the functional capacity of individual human T cells is not well defined. We studied the functional capacity of human CD4+ T-cell clones that recognize a specific mycobacterial peptide. Clone B9 produced high concentrations of IFN-gamma and exhibited potent CTL activity, whereas clone D3 produced IFN-gamma but showed poor CTL activity. The CTL activity of clone B9 was inhibited by SrCl(2) and concanamycin A but not by anti-Fas antibodies. Clone B9 also reduced the mycobacterial burden in dendritic cells by more than 90%, and this antimycobacterial activity was inhibited by SrCl(2) and concanamycin A. We conclude that: (1) individual human peptide-specific CD4+ T-cell clones have differential capacity to produce Th1 cytokines and to lyse M tuberculosis-infected target cells; and (2) both granulysin and perforin contribute to the capacity of human CD4+ T-cells to lyse infected targets and to inhibit intracellular mycobacterial growth.
Klucar
Peter
P
Department of Microbiology and Immunology, University of Texas Health Center at Tyler, Tyler, TX, USA.
Barnes
Peter F
PF
Kong
Ying
Y
Samten
Buka
B
Tvinnereim
Amy
A
Spallek
Ralf
R
Nepom
Gerald T
GT
Singh
Mahavir
M
Shams
Homayoun
H
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000382:microbiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D018942:Macrolides / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D054353:Perforin / Q000502:physiology
D000945:Antigens, Differentiation, T-Lymphocyte; D001426:Bacterial Proteins; D016207:Cytokines; C075005:GNLY protein, human; D018942:Macrolides; D010446:Peptide Fragments; D054353:Perforin; C036978:concanamycin A; D007371:Interferon-gamma