Differential susceptibility of naïve and activated human gammadelta T cells to activation-induced cell death by T-cell receptor cross-linking.
BACKGROUND
T cells undergo activation-induced cell death (AICD) through repeated stimulation of their T cell receptors (TCRs). Activated human gammadelta T cells were found to die by apoptosis when their TCRs were cross-linked by antibodies, whereas naïve gammadelta T cells freshly isolated from blood did not. Therefore, we investigated the factors that could contribute to this differential susceptibility.


METHODS
Gammadelta T cells were isolated from the peripheral blood of healthy human volunteers and their TCRs were cross-linked either directly (naïve) or after an in vitro incubation of 11 days (activated). Their cell cycle profiles, cytokine, Fas and FasL mRNA messages, and surface expression of Fas and FasL were determined.


RESULTS
The naïve cells were cycling while the activated T cells exited from the G1 to subG1 phase upon TCR cross-linking. IL-2 and IL-4 mRNAs and surface expression of FasL were detected only in activated T cells in the time period examined. In addition, cFLIP mRNA expression was found only in naïve gammadelta T cells and activated T cells treated with cyclosporin A (CsA), which inhibited AICD in the activated T cells. CsA also downregulated the surface expression of FasL in activated T cells.


CONCLUSIONS
The differential expression of cytokines, apoptotic inducers and inhibitors provide the basis for the differential susceptibility of naïve and activated gammadelta T cells to AICD upon TCR cross-linking. This contributes to our understanding of the regulation and maintenance of gammadelta T-cell homeostasis, which would be important in many infectious as well as autoimmune diseases, where gammadelta T cells have been implicated.
Gan
Y H
YH
Department of Biochemistry, National University of Singapore.
Lui
S S
SS
Malkovsky
M
M
D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D002470:Cell Survival; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor; D016572:Cyclosporine