Analysis of tolerance inducing mechanism after application of oncogen-transformed macrophages.
The purpose of this study was to examine the expression of T cell receptors (TCR) and their V beta subclasses under the influence of the parental cell line P388D1 and its clones mos2 and mos3, using a mouse model. It was shown, that v-mos oncogene-transformed cells of this line (mos2) induced selective immunological unresponsiveness in vitro. Because the induction of tolerance is of a central importance for the organ transplantation, this phenomenon, found in vitro, was also studied in vivo. We found that the in vivo injection of mos2 cells into mice induced a state of selective noncreativity. To further analyse these effects, we studied whether specific tolerance is the consequence of a decreased number of essential receptors or receptor families. For this purpose C57BL/6 mice were immunized with cells of the parental line P388D1 or mos2 and mos3 clones. Their spleen and thymus cells were examined phenotypically. The most impressive result of this study was a clearly changed amount of T cells receptors in mos2 immunized mice, in which a state of tolerance was induced. In these mice only the expression of CD3 T receptors as well as that of the V beta 11 chains was reduced. In spleen of these mice the CD3 expression was decreased, compared to D1 or nonimmunized control animals by 54-58% and compared to mos3 mice by 38-40%. Even though the differences in the thymus were not very pronounced, we still saw a decrease in CD3 stained cells selective in mos2 immunized C57B1/6. The expression of V beta 11 chains on the surface of spleen cells of mos2 animals was reduced by 33.3%, on the thymocytes even by 50% comparing to that in nonimmunized mice. Whether the reduced expression of T receptor V beta families is due to changes in the genetic material (cDNA), has to be studied.
Institute of Immunology, Christian Albrechts University, Kiel, Germany.
A M
AM
Waaga
J M
JM
Otte
M
M
Krzymański
V
V
Eckstein
W
W
Müller-Ruchholtz
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002461:Cell Line, Transformed; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D015151:Immunoblotting / Q000379:methods; D007942:Leukemia, Experimental; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009693:Nucleic Acid Hybridization / Q000379:methods; D009857:Oncogenes / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013194:Staining and Labeling / Q000379:methods; D014184:Transplantation, Homologous / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta