Activation of cord T lymphocytes. II. Cellular and molecular analysis of the defective response induced by anti-CD3 monoclonal antibody.
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.
Bertotto
A
A
Department of Pediatrics, University of Perugia, Italy.
Gerli
R
R
Lanfrancone
L
L
Crupi
S
S
Arcangeli
C
C
Cernetti
C
C
Spinozzi
F
F
Rambotti
P
P
D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D000001:Calcimycin / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate