T-lymphocyte calcium influx characteristics and their modulation by Kv1.3 and IKCa1 channel inhibitors in the neonate.
Cytokine production in activated T lymphocytes of the term neonate is reduced compared with adults. We aimed to characterize the calcium influx kinetics of activated T lymphocytes in the neonate and to test the functionality and expression of Kv1.3 and IKCa1 lymphocyte potassium channels, important regulators of calcium influx. We isolated lymphocytes from the peripheral blood of nine adults and cord blood of nine term neonates. We measured the calcium influx kinetics with flow cytometry in the T(h)1, T(h)2, CD4 and CD8 T-lymphocyte subsets activated with PHA. We determined the sensitivity of calcium influx to specific inhibitors of the Kv1.3 and IKCa1 channels. We also measured Kv1.3 channel expression using specific antibody. With the exception of the CD4 subset, calcium influx kinetics was decreased upon activation in neonatal T lymphocytes compared with adults. Neonatal T lymphocytes were found to be less sensitive to the specific inhibition of Kv1.3 and IKCa1 channels. The expression of Kv1.3 channels was higher on major T-lymphocyte subsets of newborns except for T(h)1 lymphocytes. Our findings suggest that the characteristics of short-term activation of major neonatal T-lymphocyte subsets are altered compared with adults. The altered function of neonatal lymphocyte potassium channels may contribute to this phenomenon.
Toldi
Gergely
G
First Department of Pediatrics, Semmelweis University, Bókay u. 53-54, Budapest H-1083, Hungary. toldigergely@yahoo.com
Treszl
András
A
Pongor
Vince
V
Gyarmati
Béla
B
Tulassay
Tivadar
T
Vásárhelyi
Barna
B
D000328:Adult; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D056747:Immunomodulation; D007231:Infant, Newborn / Q000276:immunology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D051664:Kv1.3 Potassium Channel; D011720:Pyrazoles; D012604:Scorpion Venoms; C411671:TRAM 34; C077910:margatoxin