CD3 antigen-mediated calcium signals and protein kinase C activation are higher in CD45R0+ than in CD45RA+ human T lymphocyte subsets.
T lymphocytes may be separated into subsets according to their expression of CD45 isoforms. The CD45R0+ T cell subset has been reported to proliferate in response to recall antigen and to mitogenic mAb to a much greater extent than the CD45RA+ subset. This difference could be due to more efficient coupling of the T cell antigen receptor complex to mitogenic signaling pathways. To investigate this possibility, CD3 antigen-induced calcium signals, diacylglycerol (DAG) production and protein kinase C (PKC) activation levels were compared in CD45RA+ and CD45R0+ human T lymphocyte subsets derived from peripheral blood. The mean CD3-induced rise in intracellular calcium was 80% greater in CD45R0+ than in CD45RA+ cells. Basal DAG levels in CD45R0+ cells were found to be, on average, 60% higher than in CD45RA+ cells (p = 0.002), but the CD3-induced production of DAG over background was not different in the two subsets (p = 0.4). Basal PKC activity, and CD3-induced PKC activation levels over background, were found to be 50% and 140% higher, respectively, in CD45R0+ cells than in CD45RA+ cells (p = 0.015 and 0.023). The CD45R0+ subset contained a higher proportion of cells expressing activation markers, such as CD25, CD71 and major histocompatibility complex class II, when compared to the CD45RA+ subset. Our results suggest that the elevated basal DAG levels observed in the CD45R0+ subset may reflect the recent activation of these cells. Both the higher basal DAG and CD3-induced elevation in intracellular calcium observed in the CD45R0+ cells may contribute to the greater PKC activation signals triggered by CD3 mAb in this subset. These findings elucidate the greater response of CD45R0+ T cells to mitogenic stimuli compared to CD45RA+ cells.
Robinson
A T
AT
Department of Immunology, Institute of Animal Physiology & Genetics Research, Babraham, Cambridge.
Miller
N
N
Alexander
D R
DR
D000328:Adult; D017252:CD3 Complex / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004075:Diglycerides / Q000096:biosynthesis; D004789:Enzyme Activation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000502:physiology*
D017252:CD3 Complex; D004075:Diglycerides; D011493:Protein Kinase C; D017493:Leukocyte Common Antigens; D002118:Calcium