C-kit+ FcR+ myelocytes are increased in cancer and prevent the proliferation of fully cytolytic T cells in the presence of immune serum.
Immunogenic cancers induce both IgG antibodies and CD8(+) cytotoxic T lymphocytes (CTL). Rejection of almost all immunogenic tumors depends ultimately on CTL. When tumors grow progressively, IgG continues to be produced but CTL may no longer be demonstrable. Using syngeneic mixed lymphocyte tumor cell cultures, we found that proliferation of fully activated proliferating CTL is prevented by a small subpopulation of immature myeloid c-kit(+) FcR(+) cells, for convenience referred to as "barrier cells". Both, FcR on barrier cells and IgG linked to TGF-beta (IgG-TGF-beta) present in immune serum, are obligatory for barrier cells to prevent proliferation of CTL, suggesting that IgG-TGF-beta binds FcR to activate suppression. Growing tumors increase barrier cells in the spleen. Interfering with the cells or molecules essential for barrier cells to prevent proliferation of CTL may enhance tumor and other CD8(+) CTL-mediated immunity.
Beck
Christian
C
The Department of Pathology, The University of Chicago, Chicago, USA. c.beck@med2.uni-kiel.de
Schreiber
Karin
K
Schreiber
Hans
H
Rowley
Donald A
DA
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D007106:Immune Sera / Q000276:immunology*; D007165:Immunosuppression Therapy; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; C501470:FcRI protein, mouse; D007106:Immune Sera; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D019009:Proto-Oncogene Proteins c-kit