title: T-cell response to phorbol ester PMA and calcium ionophore A23187 in Down's syndrome.
abstract: The proliferative response of purified T cells to anti-CD2 monoclonal antibodies (T112 plus T113) was found to be markedly reduced in 12 subjects with Down's syndrome (DS). The addition of phorbol ester PMA, which activates Ca2+/phospholipid-dependent enzyme protein kinase C, or calcium ionophore A23187, which increases intracytosolic free Ca2+ concentration, enhanced, but did not normalize, the defective anti-CD2-mediated T-cell mitogenesis. In contrast, the proliferation of resting lymphocytes from trisomic patients was comparable to that of the control cells when PMA and A23187 were used as co-blastogenic reagents. Because PMA and A23187 together bypass the early activation pathways and promote T-cell growth through the direct induction of membrane interleukin 2 (IL-2) receptor expression and IL-2 synthesis and secretion, it could reasonably be hypothesized that the faulty DS T-cell activation induced by antigen or mitogen is due to a deranged transmembrane signal transduction, rather than a defect in the later intracellular events.
authors.affiliation: Department of Paediatrics, Perugia University Medical School, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bertotto
authors.forename: S
authors.initials: S
authors.lastname: Crupi
authors.forename: C
authors.initials: C
authors.lastname: Arcangeli
authors.forename: R
authors.initials: R
authors.lastname: Gerli
authors.forename: F
authors.initials: F
authors.lastname: Scalise
authors.forename: G
authors.initials: G
authors.lastname: Fabietti
authors.forename: E
authors.initials: E
authors.lastname: Agea
authors.forename: R
authors.initials: R
authors.lastname: Vaccaro
mesh_terms: D000293:Adolescent; D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018801:CD2 Antigens; D000001:Calcimycin / Q000494:pharmacology*; D002648:Child; D004314:Down Syndrome / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D011971:Receptors, Immunologic; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate