DESTRUCTION OF HEMATOPOIETIC MICROENVIRONMENT BY CYTOTOXIC T-CELLS

Coculture of cytotoxic T cells (STIL-3 C5) derived from L8313 leukemic mice with hematopoietic supportive stromal cells (MS-5) resulted in t he detachment of MS-5 cells from the culture dish, whereas helper T ce lls (STIL-3 DF) did not induce this detachment. The response of bone m arrow (BM) adherent ent cells to the same treatment was similar to tha t of MS-5 cells. The detached cells were unable to proliferate further , and genomic DNA of these cells showed fragmentation, suggesting that hematopoietic stromal cells died of apoptosis. Reverse transcriptase- polymerase chain reaction (RT-PCR) analysis revealed that STIL-3 C5 ce lls, but not STIL-3 DF cells expressed perforin, granzyme A & B, and F as ligand. Fas was expressed in MS-5, BM adherent cells, MS-K and NIH/ 3T3 cells, which do not support hematopoiesis. These data suggest that the aforementioned factors mediate induction of apoptosis in MS-5 cel ls induced by direct cell-to-cell interaction with STIL-3 C5. This may explain the mechanism responsible for the destruction of the hematopo ietic microenvironment by cytotoxic T cells in L8313 leukemia, from wh ich STIL-3 cells are derived; it also suggests that destruction of hem atopoietic tissue may be caused by leukemic cytotoxic T cells in some cases of leukemia.