Tumorigenicity of mouse T lymphoma cells is controlled by the level of major histocompatibility complex class I H-2Kk antigens.
We have previously found that an increased tumorigenicity and spontaneous metastatic potential of BW5147-derived T lymphoma cells was associated with a decrease in major histocompatibility complex (MHC) class I H-2Kk antigen expression. This suggested that H-2Kk antigens may control the tumorigenic potential of BW T lymphoma cells. Our current experiments aimed to prove this association by specifically altering H-2Kk expression by gene transfection. Transfected cells expressing a high level of H-2Kk antigens were significantly less tumorigenic and metastatic after subcutaneous inoculation. However, there was selection in vivo for cells expressing a reduced level of H-2Kk antigens, which concomitantly led to an increased tumorigenicity. These data further confirmed the strong association between H-2Kk expression and tumorigenicity. We subsequently tested whether the immune system is implicated in this phenomenon by inoculating the H-2Kk transfectants into irradiated, immunocompromised recipients. Our results indicate that the reduced tumorigenicity of the BW H-2Kk transfectants is due to an immune rejection mechanism, mediated by CD8+ immune effector cells, as revealed by in vivo depletion experiments with anti-CD8 antibodies. Hence, we hereby demonstrated that H-2Kk antigens increased the immunogenicity of BW cells, via a CD8-dependent mechanism, which consequently reduced their tumorigenicity.
VandenDriessche
T
T
Laboratory of Cellular Immunology, Free University of Brussels, Belgium.
Bakkus
M
M
Toussaint-Demylle
D
D
Thielemans
K
K
Verschueren
H
H
De Baetselier
P
P
D000818:Animals; D015139:Blotting, Southern; D016827:CD8 Antigens / Q000032:analysis; D002460:Cell Line; D006183:H-2 Antigens / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008212:Lymphocyte Depletion; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000502:physiology; D014162:Transfection
D016827:CD8 Antigens; D006183:H-2 Antigens; C024755:H-2K(K) antigen