M. Bochan et al., TARGET CELL-DIRECTED DEGRADATION OF PERFORIN MESSENGER-RNA IN CTL - LACK OF CORRELATION WITH LOSS OF PROTEIN AND LYTIC ABILITY, Molecular immunology, 31(5), 1994, pp. 401-410
We have previously shown that CTL and NK cells rapidly down regulate p
erforin mRNA and become functionally inactive within 4-6 hr after expo
sure to sensitive target cells (TC). We report here for the first time
that CTL also down regulate perforin mRNA upon exposure to resistant,
but binding, TC. When three separate human MHC-restricted CTL lines w
ere exposed to resistant TC, perforin mRNA was rapidly degraded. Remov
al of both extracellular Ca++ and Mg++ prevented perforin message down
regulation, whereas removal of Ca++ alone did not, indicating that CT
L: TC binding was required. Unlike the response of CTL exposed to sens
itive TC, resistant TC did not trigger serine esterase (SE) release, s
uggesting distinct signalling pathways for perforin mRNA down regulati
on and granule exocytosis. Moreover, using western analysis, we showed
that there was limited (< 10%) perforin protein release after CTL: TC
interaction, suggesting that CTL loss of lytic activity after exposur
e to sensitive TC is not due to massive depletion of perforin. Treatme
nt of CTL with mAb to CD2, CD3, CD2 + CD3, CD8, Class I and LFA-1 did
not induce perforin mRNA down regulation. Furthermore, mAb to CD2, CD3
, CD8, Class I, Class II, CD54 and LFA-1 did not block TC-mediated per
forin mRNA down regulation although lysis of TC was inhibited.