Differential ability of T cell subsets to undergo activation-induced cell death

Abstract

Human T cell clones were analyzed for their susceptibility to activation-induced cell death (AICD) in response to CD3͞T cell receptor ligation. AICD was observed only in Th1 clones and was Fas-mediated, whereas Th2 clones resisted AICD. Analysis of a panel of Th0 clones, characterized by their ability to secrete both Th1 and Th2 cytokines, revealed that this subset included both AICD-sensitive (type A) and -resistant (type B) clones. Resistance to AICD by Th2 and Th0-type B clones was not due to lack of expression of either Fas receptor or its ligand. Paradoxically, the AICDresistant clones were susceptible to apoptosis when Fas receptor was directly ligated by anti-Fas antibodies. However, prior activation of the resistant clones by monoclonal antibodies to CD3͞TCR complex induced resistance against Fasmediated apoptosis. Thus, the Fas-FasL pathway is critical for the induction of AICD in T cells, and moreover this pathway can be negatively regulated in the AICD-resistant clones by signals that are generated from ligation of the CD3͞TCR complex.

Persistence of effector memory Th1 cells is regulated by Hopx

“…The observation that in the OVA-induced arthritis model, Hopx-deficient Th1 cells persist in spleen and lymph nodes, but not in the joint, the only place where the cationized antigen is displayed, argues that also in vivo Fas-mediated apoptosis may be involved in the elimination of Hopx-deficient Th1 cells. Th1 cells have been described to be more susceptible to Fas-mediated apoptosis than Th2 [14][15][16][17] and Th17 cells [18][19][20]. However, Th1 cells can be long lived and drive chronic inflammation [6][7][8][9][10][11][12][13], and can persist as effector/memory cells efficiently [24][25][26]65].…”

“…inflammatory bowel disease [6][7][8][9], uveitis [10], EAE [11,12] and arthritis [13]. In vitro, Th1 cells are much more sensitive to Fas-mediated apoptosis than Th2 or Th17 cells [14][15][16][17][18][19][20]. In vivo, however, effector/memory Th1 cells are abundant in chronically inflamed tissue [21][22][23] and persist over long time periods [24][25][26], suggesting that their sensitivity to Eur.…”

Apoptotic Deletion of Th Cells Specific for the 19-kDa Carboxyl-Terminal Fragment of Merozoite Surface Protein 1 During Malaria Infection

“…It has been demonstrated that prolonged conjugation between effector T cells and APCs can result in apoptosis of T cells (31). Nevertheless, Th1 cells have been shown to be more susceptible to either Fas-induced (32)(33)(34) or NO-induced (35) apoptosis than Th2 cells. Because T cell lines used in the present study exhibited Th1 type, it is of interest to determine whether Th2 cells would survive better following infection.…”

Inducible resistance to Fas-mediated apoptosis in B cells

“…With time and continued stimulation, the Fas-resistant phenotype reverses, and T cells become Fas-sensitive, without any change in the elevated level of Fas expression, perhaps as a result of IL-2R signaling and alterations in the levels of Bcl-xL and FLIP, although the precise mechanism remains uncertain [76], [129][130][131][132][133]. Additional reports suggest that Fas-sensitivity is modulated in anergic T cells, memory T cells, primed T cells and Th2 cells [134][135][136][137][138][139].…”