1. Activation of cord T lymphocytes. II. Cellular and molecular analysis of the defective response induced by anti-CD3 monoclonal antibody.
- Author
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Bertotto A, Gerli R, Lanfrancone L, Crupi S, Arcangeli C, Cernetti C, Spinozzi F, and Rambotti P
- Subjects
- Antigen-Presenting Cells immunology, CD3 Complex, Calcimycin pharmacology, Gene Expression, Humans, In Vitro Techniques, Interleukin-1 pharmacology, Interleukin-2 biosynthesis, Interleukin-2 genetics, Interleukin-2 pharmacology, RNA, Messenger genetics, Receptors, Interleukin-2 genetics, Receptors, Interleukin-2 metabolism, Solubility, Tetradecanoylphorbol Acetate pharmacology, Antigens, Differentiation, T-Lymphocyte immunology, Fetal Blood cytology, Lymphocyte Activation, Receptors, Antigen, T-Cell immunology, T-Lymphocytes immunology
- Abstract
Despite the fact that the percentage of circulating CD3-positive cells is similar in cord and adult blood, the proliferative response induced by anti-CD3 monoclonal antibody (mAb) was impaired in the majority of human cord peripheral blood mononuclear cell (PBMC) samples we tested. The cell proliferative defect was associated with low interleukin 2 (IL 2) gene expression and scant IL 2 production. However, interleukin 2 receptor was fully expressed at both the mRNA and protein levels. Such a finding is consistent with the observation that exogenous recombinant IL 2 is able to boost the anti-CD3-mediated response of cord PBMC. Furthermore, when anti-CD3 and phorbol myristate acetate (PMA) were added together, they exerted a very marked synergistic effect on both the proliferation of, and IL 2 production by, cord PBMC. The addition of allogeneic antigen presenting cells plus soluble anti-CD3 or Sepharose-coupled anti-CD3 mAb to the cord T cell cultures had no significant effect on proliferation, whereas both elicited good mitogenesis of adult T cells. Moreover, addition of exogenous recombinant interleukin 1 to anti-CD3-stimulated T cells failed to trigger any proliferation in either adult or cord samples. Since the combination of PMA and calcium ionophore A23187 is effective in triggering optimal proliferation of cord T cells, the defect would seem to be associated with a failure in transmembrane transduction of the activation signals provided by the anti-CD3 stimulus for the cord T cell.
- Published
- 1990
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