The human autologous mixed lymphocyte reaction. II. Analysis of activation and proliferation

In this study, we have used cell cycle analysis as an independent measure of proliferation and the 4F2 marker to enumerate activated T cells. T-cell proliferation increased gradually throughout the 7-day culture. The degree of proliferation correlated very strongly (r = 0 . 827, p less than 10(-4)) with the degree of T-cell activation as demonstrated by the expression of the 4F2 marker. However, many more T cells became activated during the AMLR than were proliferating. Thymidine incorporation correlated well (r = 0.956, p less than 10(-4)) with numbers of proliferating cells as determined by cell cycle analysis. Adherent cells (M phi) induced fewer T cells to express 4F2 and to proliferate than did (B + null) cells. However, proportionately, M phi induced much more activation than proliferation in comparison to (B + null) cells. Additional analyses of cell cycle and the 4F2 marker for activated cells indicated that a very small percentage of responder T cells (less than 1%) respond initially to signals from autologous non-T cells. Moreover, there is a three-day delay before substantial proliferation and activation takes place, providing time for amplification and suppressive regulatory processes. Ultimately, between 5 and 30% of the initial T cells are capable of proliferating in the AMLR and up to 90% of the cells may become activated. Thus, many cells become activated (and are therefore capable of secreting immune regulatory factors or otherwise participating in immune responses) than proliferate. These results provide a basis for analysing defects in the AMLR in association with various disease states.