Protein kinase C-dependent and -independent mechanisms of cloned murine T cell proliferation. The role of protein kinase C translocation and protein kinase C activity.
PMA can induce the proliferation of several CTL clones but not of several Th clones derived and tested in our laboratory. The PMA-stimulated proliferation of our CTL clones (which do not make IL-2 mRNA or protein) occurs independently of IL-2 and is not accompanied by lymphokine release. We now report, however, that protein kinase C (PKC) translocation is induced by PMA in CTL clones as well as in Th clones, which lack a proliferative response to PMA. These results suggest that PKC translocation itself is not a sufficient regulatory mechanism to account for cloned T cell proliferation. Moreover, IL-2 did not induce PKC translocation in a CTL clone, which proliferates when stimulated with IL-2. Thus, PKC translocation may not be necessary for activation of CTL proliferation. Nonetheless, cellular PKC activity appears to be required for the proliferative response of T cell clones after stimulation by PMA/PMA + calcium ionophore (A23187) or by triggering through the TCR: chronic PMA treatment, which depletes intracellular PKC activity, abrogates the proliferative response of T cell clones stimulated by PMA/PMA + A23187 or triggered through the TCR. T cell clones depleted of PKC activity, however, retain the ability to proliferate when challenged with IL-2. Murine T cell clones, therefore, possess PKC-dependent and PKC-independent pathways of proliferation that are not regulated by PKC translocation alone.
Kim
D K
DK
Department of Pathology, Pritzker School of Medicine, Chicago, IL 60637.
Lancki
D W
DW
Hui
F H
FH
Fitch
F W
FW
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002999:Clone Cells / Q000201:enzymology / Q000276:immunology; D004075:Diglycerides / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004338:Drug Combinations; D004789:Enzyme Activation; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D004075:Diglycerides; D004338:Drug Combinations; D011948:Receptors, Antigen, T-Cell; C044295:1,2-dioctanoylglycerol; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate