International Immunology, Vol 9, 127-138, Copyright © 1997 by Oxford University Press
L Strzadala, A Miazek, J Matuszyk and P Kisielow
To investigate the role of antigen receptor-mediated interactions in
lymphomagenesis we have analyzed the influence of alpha beta TCR- mediated
selection on the development of spontaneous thymic lymphomas, which appear
with a high (up to 50%) frequency in mice expressing a transgenic TCR
specific for the male antigen (HY) in the context of H- 2Db molecules. To
this end we compared the kinetics and the incidence of thymic lymphomas
developing in females and males with selecting (H- 2b) and non-selecting
(H-2k) MHC molecules. The kinetics of development of thymic lymphomas was
similar in positively selecting (H-2b females) and non-selecting (H-2k
females and males) environments but significantly slower (P < 0.01) in
the negatively selecting environment (H-2b male). Injection of lymphoma
cells derived from a H-2b female into the thymus of a H-2b male resulted in
strong, antigen-specific inhibition of growth, indicating that the slower
kinetics of lymphomagenesis in H-2b males could be due, at least partially,
to the sensitivity of oncogenically transformed thymocytes to TCR-mediated
negative selection. Phenotypic and functional analysis of lymphoma cells
indicated that they originated from the stage of pre-TCR- dependent
transition of immature CD4-CD8- to CD4+ CD8+ thymocytes, which in H-2b
females and males developed into tumors under different environmental
pressures. These results failed to provide convincing evidence for the role
of positive selection but provided a strong indication that self
antigen-induced negative selection, in addition to its well established
role in self tolerance, can occasionally act as a tumor surveillance
mechanism by eliminating or suppressing growth of thymocytes undergoing
oncogenic transformation.
ARTICLES
Role of thymic selection in the development of thymic lymphomas in TCR transgenic mice
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
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