Evidence for human CD4+ T cells in the CD1-restricted repertoire: derivation of mycobacteria-reactive T cells from leprosy lesions.
Both the CD4-CD8- (double negative) and CD4-CD8+ T cell lineages have been shown to contain T cells which recognize microbial lipid and glycolipid Ags in the context of human CD1 molecules. To determine whether T cells expressing the CD4 coreceptor could recognize Ag in the context of CD1, we derived CD4+ T cell lines from the lesions of leprosy patients. We identified three CD4+ Mycobacterium leprae-reactive, CD1-restricted T cell lines: two CD1b restricted and one CD1c restricted. These T cell lines recognize mycobacterial Ags, one of which has not been previously described for CD1-restricted T cells. The response of CD4+ CD1-restricted T cells, unlike MHC class II-restricted T cells, was not inhibited by anti-CD4 mAb, suggesting that the CD4 coreceptor does not impact positive or negative selection of CD1-restricted T cells. The CD4+ CD1-restricted T cell lines produced IFN-gamma and GM-CSF, the Th1 pattern of cytokines required for cell-mediated immunity against intracellular pathogens, but no detectable IL-4. The existence of CD4+ CD1-restricted T cells that produce a Th1 cytokine pattern suggests a contributory role in immunity to mycobacterial infection.
Sieling
P A
PA
Division of Dermatology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA. psieling@mednet.ucla.edu
Ochoa
M T
MT
Jullien
D
D
Leslie
D S
DS
Sabet
S
S
Rosat
J P
JP
Burdick
A E
AE
Rea
T H
TH
Brenner
M B
MB
Porcelli
S A
SA
Modlin
R L
RL
D017951:Antigen Presentation; D000941:Antigens / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type; D007918:Leprosy / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D009166:Mycobacterium leprae / Q000276:immunology*; D009171:Mycolic Acids / Q000276:immunology / Q000378:metabolism; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins; D011971:Receptors, Immunologic / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology
D000941:Antigens; D000942:Antigens, Bacterial; D018949:Antigens, CD1; D000954:Antigens, Surface; D015704:CD4 Antigens; D006017:Glycolipids; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D009171:Mycolic Acids; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010455:Peptides; D011506:Proteins; D011971:Receptors, Immunologic; C048938:glucose mycolate; C050016:lipoarabinomannan