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The tumour associated cell surface antigen A6H is costimulatory for human CD4 + but not CD8 + T cells
Author(s) -
LABUDA T.,
PARRA E.,
HEDLUND G.,
KALLAND T.,
DOHLSTEN M.
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.1365-2567.1997.00149.x
Subject(s) - biology , microbiology and biotechnology , cytotoxic t cell , cd80 , il 2 receptor , interleukin 21 , cd86 , antigen presenting cell , t cell , cd8 , antigen , cytokine , cd40 , immunology , immune system , biochemistry , in vitro
The A6H monoclonal antibody (mAb) recognizes a 120 000–140 000 MW antigen that is expressed at similar densities on 85–90% of human CD4 + and CD8 + T cells and on renal cell carcinomas. The binding of the A6H mAb induced a costimulatory signal in anti‐CD3 activated T cells. In the present report, we show that A6H costimulated cell proliferation and cytokine production in purified CD4 + T cells. Unexpectedly, the CD8 + T‐cell subpopulation failed to respond. CD4 + T cells costimulated with the A6H mAb upregulated CD80, CD86, CD71, interleukin‐2 (IL‐2)R α , IL‐2R β and IL‐2R γ , while no corresponding up‐regulation of these cell surface molecules was seen in CD8 + T cells. In order to investigate the nature of the A6H mAb costimulus at the transcriptional level we have examined induction of the transcription factors OCT‐1, AP‐1 and NF‐ κ B which are known to be transcriptional regulators of several cytokine and cytokine receptor genes, including the IL‐2 and IL‐2R genes. Co‐ligation of the A6H antigen and the CD3 complex induced expression of the transcription factor AP‐1 in CD4 + T cells, whereas no increase in NF‐ κ B and octamer‐binding (Oct) proteins was seen compared to T cells stimulated with anti‐CD3 alone. Furthermore, no induction of AP‐1 was seen in A6H costimulated CD8 + T cells. These results suggests that both proximal steps in CD8 + T‐cell activation as well as the later phases are unresponsive to A6H ligation. Molecular differences of the A6H molecule or distinct regulation of the A6H transduced AP‐1 activation pathway may exist in CD4 + and CD8 + T cell subpopulations.