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T‐Cell Response to Phorbol Ester PMA and Calcium Ionophore A23187 in Down's Syndrome
Author(s) -
BERTOTTO A.,
CRUPI S.,
ARCANGELI C.,
GERLI R.,
SCALISE F.,
FABIETTI G.,
AGEA E.,
VACCARO R.
Publication year - 1989
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1989.tb02465.x
Subject(s) - protein kinase c , ionophore , calcium , calcium in biology , intracellular , second messenger system , endocrinology , cell growth , medicine , signal transduction , microbiology and biotechnology , t cell , phorbol , biology , chemistry , biochemistry , immunology , immune system
The proliferative response of purified T cells to anti‐CD2 monoclonal anybodies (TII 2 plus TII 3 ) was found to be markedly reduced in 12 subjects with Down's syndrome (DS). The addition of phorbol ester PMA, which activates Ca 2+ /phospholipid‐dependent enzyme protein kinase C, or calcium ionophore A23187, which increases intracytosolic free Ca 2+ 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.