Increased protein kinase C activity in human memory T cells.
A number of T cell surface antigens including CD45R0, CD58, CD11 alpha, CD29, CD44, and CD26 are present on differentiated T cells and identify T cell populations that respond to recall antigens. To further study the biochemical basis for this immune memory, we used an anti-CD26 mAb to identify the memory T cell population. We have previously shown that CD26+ T cells display an increased proliferative response to anti-CD3 and anti-CD2 mAbs and furthermore have significantly greater PMA-induced phosphorylation of the invariant gamma and delta chains of the T cell receptor (TCR)/CD3 complex when compared to CD26-T cells. This suggested that differential distribution of protein kinase C (pkC) in the CD26 subsets may be related to the reduced activation requirements observed in memory T cells upon recall antigen challenge. We now directly demonstrate that when peripheral blood T cells are sorted into CD26+ and CD26- T cells the majority of pkC activity can be recovered from the cytosol fraction of the memory (CD26+) T cell population. When activated through the TCR/CD3 pathway, the CD2 pathway, or directly by the phorbol ester, PMA, the memory (CD26+) T cells showed an increased proliferative response that was inhibited by the pkC inhibitor, staurosporine. When CD26+ T cells were cultured in the presence of PMA, which depletes pkC activity, CD26 antigen expression was down-regulated. PMA was also able to inhibit phytohemagglutinin (PHA)-induced expression of the CD26 antigen in CD26- T cells. These data demonstrate a relation between CD26 expression and pkC activity and suggest that enhanced pkC activity is associated with memory T cell function.
Höllsberg
P
P
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Melinek
J
J
Benjamin
D
D
Hafler
D A
DA
D000470:Alkaloids / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000378:metabolism*; D002999:Clone Cells; D018819:Dipeptidyl Peptidase 4; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D019311:Staurosporine; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D000945:Antigens, Differentiation, T-Lymphocyte; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D011493:Protein Kinase C; D018819:Dipeptidyl Peptidase 4; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate