Article

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

Istituto di Morfologia Umana Normale, Chieti, Italy.
The Journal of Immunology (impact factor: 5.79). 10/1999; 163(5):2416-24. pp.2416-24
Source: PubMed

ABSTRACT 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. PLCbeta1 and delta1 are expressed at higher levels in cord T cells, while PLCbeta2 and gamma1 expression is higher in adult T lymphocytes. PLCdelta2 and gamma2 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 PLCgamma activation and decreased Lck expression.

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Keywords

adult T cells
 
adult T lymphocytes
 
Ca2+ mobilization
 
CD3 ligation
 
cord blood T cells
 
cord blood-derived T cells
 
cord blood-derived T lymphocytes
 
cord T cells
 
cytokine production
 
functional distinctions
 
G protein activator
 
impaired PLC activation
 
pervanadate treatment
 
pharmacologic activation
 
PLC activation
 
protein kinase C
 
protein kinase C activation
 
reduced level
 
similar degree
 
Src kinase