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 the detachment of MS-5 cells from the culture dish, whereas helper T cells (STIL-3 DF) did not induce this detachment. The response of bone marrow (BM) adherent cells to the same treatment was similar to that 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 cells, but not STIL-3 DF cells expressed perforin, granzyme A & B, and Fas 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 cells induced by direct cell-to-cell interaction with STIL-3 C5. This may explain the mechanism responsible for the destruction of the hematopoietic microenvironment by cytotoxic T cells in L8313 leukemia, from which STIL-3 cells are derived; it also suggests that destruction of hematopoietic tissue may be caused by leukemic cytotoxic T cells in some cases of leukemia.
Takashita
E
E
Department of Molecular and Cellular Biology, Faculty of Science, Niigata University, Japan.
Sugimoto
K
K
Adachi
Y
Y
Aihara
Y
Y
Inoue
H
H
Jiang
H
H
Katakai
T
T
Mori
K J
KJ
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D017209:Apoptosis; D002448:Cell Adhesion; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015870:Gene Expression; D053804:Granzymes; D006410:Hematopoiesis; D016130:Immunophenotyping; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019014:fas Receptor / Q000235:genetics
D000954:Antigens, Surface; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases