TCR V alpha 24 and V beta 11 coexpression defines a human NK1 T cell analog containing a unique Th0 subpopulation.
Murine NK1 natural T (NT) cells are a population of alphabeta T cells that express NK cell receptors and an invariant TCR rearrangement. These cells rapidly produce large amounts of IL-4 upon activation and have been suggested to promote Th2 differentiation. We sought to determine whether a human NK1 T cell analogue could be detected in PBMC, and if so, characterize the TCR usage, cytokine expression, and surface phenotype of this subset. Using flow cytometry, we have demonstrated a distinct population of V alpha24+, V beta11+, CD56+ T cells consistent with NT cells. Upon sequencing, these cells expressed an invariant V alpha24-J alphaQ TCR rearrangement, verifying their identity as a human NK1 T cell analogue. NT cells demonstrated increased frequencies of both IFN-gamma and IL-4 production. Strikingly, 30 to 45% of CD4+ NT cells expressed IL-4, a sixfold greater frequency than that seen in mainstream CD4+ alphabeta T cells. Contrary to the pattern seen with mainstream T cells, virtually all IL-4-producing NT cells coexpressed IFN-gamma, indicating that this subset of NT cells has a unique Th0 phenotype. These data establish that V alpha24+ NT cells are a potent source of IL-4 and as such, may play a role in Th2 priming in human immune responses. This work demonstrates that human NT cells can be phenotypically identified and functionally studied in the blood of healthy or diseased subjects.
Prussin
C
C
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-1881, USA. calman@nih.gov
Foster
B
B
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D000954:Antigens, Surface; D019002:CD56 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007371:Interferon-gamma