IL-2 Modulates Fas Ligand Expression In Resting But Not Activated Co-Stimulator Depleted CD4+ T-Cells Inhibiting TCR Mediated Cell Death

DJ Cohen; Y Tian; BS Ooi, Renal Section, VAMC Washington, DC and George Washington University School of Medicine

Highly purified resting and activated murine splenic CD4+ T-cells are used as in vitro surrogates for alloantigen specific unprimed and primed T-cells stimulated through the T-cell receptor (TCR) in the absence of co-stimulator signals. The ability of IL-12 to modulate TCR mediated cell death versus proliferation was studied in CD4+ T-cells in both the resting and activated state. IL-12 inhibits TCR mediated apoptosis of resting CD4+ T-cells in the absence of IL-2 and presence of anti-IL-2MAb. Activated CD4+ T-cells restimulated with anti-TCR MAb undergo apoptosis and this cell death is not inhibited by IL-12. Anti-Fas MAb (Jo2) inhibits cell death of both activated and resting CD4+ T-cells (Fig 1A & B respectively) confirming the role of Fas-FasL in this model of TCR mediated cell death. Flow cytometric analysis shows that IL-12 decreases expression of FasL but not Fas in resting CD4+ T-cells in the absence of IL-2. The expression of Fas and FasL on activated CD4+ T-cells was not affected by IL-12 nor IL-2. These data indicate that IL-12 may have an important role in the commitment to proliferation rather than deletion by death of unprimed T-cells.