T-cell response to phorbol ester PMA and calcium ionophore A23187 in Down's syndrome.
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.
Bertotto
A
A
Department of Paediatrics, Perugia University Medical School, Italy.
Crupi
S
S
Arcangeli
C
C
Gerli
R
R
Scalise
F
F
Fabietti
G
G
Agea
E
E
Vaccaro
R
R
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*
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D011971:Receptors, Immunologic; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate