Monocyte-driven activation-induced apoptotic cell death of human T-lymphotropic virus type I-infected T cells

We attempted apoptotic cell death induction of T cells infected with human T lymphotropic virus type I (HTLV-I) which induces HTLV-I-associated myelop athy/tropical spastic paraparesis and adult T cell leukemia. T cells acutel y infected and expressing HTLV-Igag Ags were killed by cross-linking their TCR with anti-CD3 mAb. Cells in apoptotic process were found by staining wi th annexin V, The apoptosis was not affected by costimulation through CD28 molecules and was resistant to ligation of Fas molecules. Whereas the virus -infected T cells expressed higher levels of HLA-DR, CD25, CD80, and CD86 A gs than apoptosis-resistant PHA-blasts, the T cell apoptosis was enhanced b y addition of exogenous IL-2. Furthermore, in this apoptosis, monocytes pla yed an important role because T cells infected in the absence of monocytes were resistant to the death signals. The apoptosis-sensitive T cells respon ded to TCR signaling more strongly by proliferating than those apoptosis-re sistant cells. Monocytes weakly affected the expression levels of viral Ags on T cells. However, HTLV-I-infected monocytes primed T cells to die by su bsequent TCR signaling, T cells primed with the monocytes, subsequently inf ected in the absence of monocytes, were killed by TCR signaling, These obse rvations suggest that primed and infected T cells could be killed by activa tion-induced cell death.