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Early biochemical events associated with lymphocyte activation in ageing. I. Evidence that Ca2+ dependent processes induced by PHA are impaired

par Kennes, Bernard ;Hubert, Claude ;Brohée, Dany ;Neve, Pierre
Référence Immunology, 42, 1, page (119-126)
Publication Publié, 1981

Article révisé par les pairs

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Résumé :

The requirement for Ca2+, a divalent ion which plays a fundamental role in cell activation, has been analysed in cultures of PHA-stimulated human peripheral blood lymphocytes (PHA-PBL) from adult (range: 20-35 years) and old (over 70 years) subjects. For this purpose, increasing concentrations of Ca2+ chelators (EGTA and EDTA) were added to cultures in order to compare the effect of progressive extracellular Ca2+ (Ca2+ [Ca2+(EC)] on [3H]-Tdr incorporation by PHA-PBL. Kinetic analysis showed that Ca2+(EC) requirement was restricted to the first 24 h after culture initation. At optimal doses of PHA, the PHA-PBL from old subjects were more sensitive than those from adult subjects to increasing concentrations of both chelators. They also required larger amounts of Ca2+ supplements to restore their normal response after total inhibition by EGTA. Furthermore, the PHA-PBL from the elderly were hypersensitive to verapamil (Isoptin), a drug which instigates a reversible inhibition of Ca2+-dependent processes associated with lymphocyte transformation, by a quite similar action to that induced by chelators. We conclude that the Ca2+-dependent processes in lymphocyte activation are impaired with ageing. Following further experiments and recent work suggesting that lymphocytes need more than one signal to proliferate, the authors speculate on a deficiency of a late activation signal requiring cell-cell interactions in the elderly.