Inverse relationship of CA2+ mobilization and cell proliferation in CD8+ memory and virgin T cells

Publisher Website
Google Scholar
Abstract
Memory T cells can now be defined with various monoclonal antibodies but little is known about the functional properties of these cells as compared to virgin T cells. We have studied Ca2+ mobilization and proliferation of memory and virgin cells in both the CD4 and CD8 subsets in response to phytohemagglutinin. Using two‐color fluorescence (yellow, red) for cell surface staining combined with two‐color fluorescence for the Ca2+ chelator indo‐1 (violet, blue) we can demonstrate that CD8+UCHL1+ memory cells exhibit a 1,5‐fold higher influx than the CD8+UCHL1− virgin cells. The same pattern was obtained when CD8 memory and virgin cells were defined by a reciprocal marker (Leu‐18) indicating that the higher response of memory CD8 cells is independent of the monoclonal antibody used to identify the cells. For the respective CD4 subsets no such clear‐cut pattern of Ca2+ influx was evident. Analysis of proliferation in both subsets indicates that CD8+UCHL1− cells strongly proliferate in response to PHA, while CD8+UCHL1+ memory cells show only a minimal response with the average cpm values being 6‐fold lower. In some instances no proliferation at all was detectable in the CD8+UCHL1+ cells. Identification of the subsets by reciprocal markers confirmed the lower proliferative response in the CD8 memory cells. Hence, within the CD8 compartment the memory cells, after phytohemagglutinin stimulation, exhibit a high Ca2+ mobilization but a low to absent proliferation, while the converse is true for the naive cells. These data show that (a) Ca2+ mobilization and proliferation are inversely correlated and (b) an initially vigorous response of memory cells may be subject to negative control mechanisms.