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- Title
The tumour associated cell surface antigen A6H is costimulatory for human CD4<sup>+</sup> but not CD8<sup>+</sup> T cells.
- Authors
Labuda, T.; Parrais, E.; Hedliund, G.; Kalland, T.; Dohlstenst, M.
- Abstract
The A6H monoclonal antibody (mAb) recognizes a 120000–140000 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)Ra, IL-2Rβ and IL-2Rγ, 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-κB 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-κB 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.
- Subjects
CELL surface antigens; TUMOR immunology; T cells; RENAL cell carcinoma; INTERLEUKIN-2; IMMUNOLOGY
- Publication
Immunology, 1997, Vol 90, Issue 2, p236
- ISSN
0019-2805
- Publication type
Article
- DOI
10.1046/j.1365-2567.1997.00149.x