Role of thymic selection in the development of thymic lymphomas in TCR transgenic mice.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Role of thymic selection in the development of thymic lymphomas in TCR transgenic mice.

Int Immunol. 1997 Jan;9(1):127-38. Unique Identifier : AIDSLINE MED/97196865
Strzadala L; Miazek A; Matuszyk J; Kisielow P; Institute of Immunology and Experimental Therapy, Polish Academy of; Sciences, Wroclaw, Poland.

Abstract: 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.

Keywords: *Lymphoma/ETIOLOGY *Receptors, Antigen, T-Cell/GENETICS *Thymus Neoplasms/ETIOLOGY
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