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Inefficient Phospholipase C Activation and Reduced Lck Expression Characterize the Signaling Defect of Umbilical Cord T Lymphocytes¹

Sebastiano Miscia^2,*, Angela Di Baldassarre^*, Giuseppe Sabatino, Ezio Bonvini^¶, Rosa Alba Rana^*, Marco Vitale^§, Valentina Di Valerio^* and Francesco Antonio Manzoli

^* Istituto di Morfologia Umana Normale, Chieti, Italy; Cattedra di Neonatologia, Università degli Studi "G. D’Annunzio," Chieti, Italy; Istituto di Anatomia Umana Normale, Università di Bologna, Bologna, Italy; ^§ Dipartimento di Scienze Biomediche e Biotecnologie, Sezione di Anatomia Umana, Università di Brescia, Brescia, Italy; and ^¶ Laboratory of Immunobiology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Bethesda, MD 20852

Adult and neonatal immunocompetent cells exhibit important functional distinctions, including differences in cytokine production and susceptibility to tolerance induction. We have investigated the molecular features that characterize the immune response of cord blood-derived T lymphocytes compared with that of adult T lymphocytes. Our findings demonstrate that phospholipase C (PLC) isozymes, which play a pivotal role in the control of protein kinase C activation and Ca²⁺ mobilization, are differently expressed in cord and adult T lymphocytes. PLCß1 and 1 are expressed at higher levels in cord T cells, while PLCß2 and 1 expression is higher in adult T lymphocytes. PLC2 and 2 appear to be equally expressed in both cell types. In addition, a functional defect in PLC activation via CD3 ligation or pervanadate treatment, stimuli that activate tyrosine kinases, was observed in cord blood T cells, whereas treatment with aluminum tetrafluoride (AlF₄^-), a G protein activator, demonstrated a similar degree of PLC activation in cord and adult T cells. The impaired PLC activation of cord blood-derived T cells was associated with a a very low expression of the Src kinase, Lck, along with a reduced level of ZAP70. No mitogenic response to CD3 ligation was observed in cord T cells. However, no signaling defect was apparent downstream of PLC activation, as demonstrated by the mitogenic response of cord T cells to the pharmacologic activation of protein kinase C and Ca²⁺ by treatment with PMA and ionomycin. Thus, neonatal cord blood-derived T cells show a signaling immaturity associated with inadequate PLC activation and decreased Lck expression.

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