Inefficient phospholipase C activation and reduced Lck expression characterize the signaling defect of umbilical cord T lymphocytes

Adult and neonatal immunocompetent cells exhibit important functional disti nctions, including differences in cytokine production and susceptibility to tolerance induction, We have investigated the molecular features that char acterize the immune response of cord blood-derived T lymphocytes compared w ith that of adult T lymphocytes, Our findings demonstrate that phospholipas e C (PLC) isozymes, which play a pivotal role in the control of protein kin ase C activation and Ca2+ mobilization, are differently expressed in cord a nd adult T lymphocytes. PLC beta 1 and delta 1 are expressed at higher leve ls in cord T cells, while PLC beta 2 and gamma 1 expression is higher in ad ult T lymphocytes, PLC delta 2 and gamma 2 appear to be equally expressed i n both cell types, In addition, a functional defect in PLC activation via C D3 ligation or pervanadate treatment, stimuli that activate tyrosine kinase s, was observed in cord blood T cells, whereas treatment with aluminum tetr afluoride (AlF4-), a G protein activator, demonstrated a similar degree of PLC activation in cord and adult T cells. The impaired PLC activation of co rd 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 respons e to CD3 ligation was observed in cord T cells, However, no signaling defec t was apparent downstream of PLC activation, as demonstrated by the mitogen ic response of cord T cells to the pharmacologic activation of protein kina se C and Ca2+ by treatment with PM and ionomycin. Thus, neonatal cord blood -derived T cells shown a signaling immaturity associated with inadequate PL C gamma activation and decreased Lck expression.