ANTIGEN-INDUCED DEATH OF ALLOREACTIVE HUMAN T-LYMPHOCYTES OCCURS IN THE ABSENCE OF LOW-MOLECULAR-WEIGHT DNA FRAGMENTATION

Stimulation via the CD3/TCR molecular complex induces proliferation of resting T cells, but triggers programmed cell death (apoptosis) in im mature thymocytes and preactivated mature T cells. Activation-induced cell death (AICD) triggered by anti-CD3/TCR mAb or by staphylococcus e nterotoxin superantigen is associated with fragmentation of genomic DN A into oligonucleosomal fragments of 200 bp length, thus displaying th e characteristic features of apoptosis. Here, we show that a fraction (20-50%) of cells in alloreactive CDS human short-term T cell lines, g enerated by repeated restimulation with EBV-transformed B cell lines, undergo AICD when restimulated with the appropriate (but not with thir d party) stimulator cells. AICD of responder T cells is inhibited when stimulator cells are preincubated with anti-HLA class I mAb but not w ith anti-HLA class II mAb, indicating that T cell death is dependent o n alloantigen (HLA class I) recognition by responding CD8 T cells. Imp ortantly, alloantigen-induced T cell death occurs in the absence of de tectable DNA fragmentation. Thus, several independent assay systems al l failed to reveal low molecular weight DNA fragmentation, even though DNA fragmentation was readily detected in T cell lines exposed to PHA or gamma-irradiation. Alloantigen-induced T cell death was prevented by aurintricarboxylic acid, which has previously been shown to inhibit apoptosis in experimental systems where no DNA fragmentation occurs. Taken together, these results demonstrate that alloantigen can trigger AICD in mature responding T cells in the absence of low molecular wei ght DNA fragmentation. (C) 1995 Academic Press, Inc.