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Massive production of Th2 cytokines by human CD4 + effector T cells transiently expressing the natural killer cell marker CD57/HNK1
Author(s) -
BRINKMANN V.,
KRISTOFIC C.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00298.x
Subject(s) - cd28 , biology , interleukin 21 , t cell , t cell receptor , natural killer t cell , il 2 receptor , cytotoxic t cell , cd3 , cytokine , microbiology and biotechnology , zap70 , interleukin 4 , immunology , cd8 , antigen , immune system , in vitro , biochemistry
We have reported previously that uncommitted human CD4 + CD45RO − T cells default to the T‐helper type 1 (Th1) pathway, if they are costimulated by anti‐CD3 plus anti‐CD28 monoclonal antibodies (mAb). In contrast, 5% of the uncommitted T cells differentiate into Th2 cells, if they are stimulated by anti‐CD28 plus interleukin‐2 (IL‐2) in the absence of T‐cell receptor (TCR) signals. The anti‐CD28/IL‐2‐induced proliferation (and the resulting Th2 commitment) was not affected by neutralizing anti‐IL‐4 mAb, suggesting a non‐conventional IL‐4‐independent Th2 differentiation pathway. Here we report that the respective CD4 + Th2 cells (but not the Th1 cells) coexpressed the natural killer (NK) cell marker HNK1/CD57. Expression of CD57 on Th2 cells required CD28 stimulation, and was suppressed by CD3/TCR signals. However, Th2 effector cells displayed a TCR V & beta;‐chain usage comparable to that of committed Th1 cells (with V & beta;8 dominating). Our data suggest that expression of CD57 on human CD4 T cells may be associated with defined stages of Th2 cell activation/differentiation, and may not necessarily characterize a separate T‐cell lineage. The induction of cytokine production and B‐cell helper function in both Th1 and Th2 populations required CD3/TCR signalling in costimulation with anti‐CD28 or IL‐2. Importantly, anti‐CD28/IL‐2‐primed Th2 cells readily secreted IL‐4 and induced IgE production by surface IgE − B cells in response to the first TCR signal and independent of previous contact with IL‐4. Therefore, CD4 + CD57 + T cells responded comparably to murine CD4 + NK1.1 + T cells, which are critical for the development of Th2/IgE immune responses in vivo . The possible role of human CD4 + CD57/HNK1 + Th2‐like cells in cancer, infection and allergy is discussed.