부산대학교 도서관

The Leu-8/TQ1 antigen, recently shown to be the human equivalent of the murine MEL-14 lymph node homing receptor and now designated as leucocyte-endothelial cell adhesion molecule, LECAM-l, has been used to dissect T, B and natural killer (NK) cells into various subpopulations with different functional properties, such as suppressor-inducer (CE4+ Leu-8/TQ1+) or helper (CD4+ Leu-8/TQ1-) T lymphocytes. Diminished Leu-8/TQ1 antigen density has been reported after lymphocyte activation with B- or T-cell specific stimuli for several days. In the present study, we sought to determine the signal requirements for altered Leu-8/TrQ1 expression. Exposure of freshly isolated peripheral blood lymphocytes to phorbol 12-myristate 13-acetate (PMA) and/or calcium ionophores was found to cause rapid down-regulation of the Leu-8 antigen, with little or no Leu-8 reactivity remaining I hr after simultaneous addition of PMA and calcium ionophores to the culture medium. TQ1 reactivity was changed in parallel with that of Leu-8. Leu-8 expression oft and B cells was sensitive to both PMA and calcium ionophores, whereas Leu-8 expression of NK cells was affected by PMA but not by the calcium ionophore A23187. The effect of PMA on Leu-8/TQ1 expression could be antagonized by pretreatment with the protein kinase C inhibitor, H7, whereas that of A23187 could not. Partial re-expression of the Leu-8 antigen was seen 3 days after addition of PMA alone but not when it was given together with calcium ionophores. After Leu-8 down regulation induced by I hr treatment with PMA or calcium ionophores, Leu-8 re-expression was observed within 24 hr when stimuli were removed by washing. Activation oft cells with anti-CD3 antibody resulted in a partial reduction of Leu-8/TQ1 expression, first detectable after 1-3 hr of stimulation and maximal at 24 hr. Fully mitogenmic concentrations of concanavalin A (Con A) did not affect Leu-8 expression within the first hours of culture. Transient reduction of Leu-8 expression was seen 24 hr after supraoptimal dosages of Con A, but Con A-stimulated lymphocytes cultured for 4-12 days with interleukin-2 (IL-2) retained Leu-8/TQ1 reactivity to a similar degree as fresh cells. In contrast to Leu-8/TQ1, CD45RA expression was not altered after I hr treatment with PMA and/or calcium ionophores but gradually disappeared during I week after Con A stimulation. Thus, Leu-8/ TQ1+ CD45RA+ lymphocytes could be rapidly converted into Leu-8/TQ1 CD45RA+ cells by PMA and/or calcium ionophores in vitro within 1 hr, whereas Leu-8/TQ1+ CD45RA- cells were generated by Con A stimulation over several days. [ABSTRACT FROM AUTHOR]