APPARENT BYPASS OF NEGATIVE SELECTION IN CD8(-MYC TRANSGENIC MICE() TUMORS IN CD2)

A role for antigen stimulation in lymphoid neoplasia has been postulat ed and is supported by indirect evidence that suggests that the intera ction of antigen with both T cells and B cells may constitute an epige netic event that can contribute to tumour induction or tumour progress ion. Using myc-bearing transgenic mice that develop mainly clonal T-ce ll lymphomas we have investigated the possibility that endogenous anti gen-mediated clonal deletion might be overridden in tumorigenesis. CD2 -mye transgenic mice were backcrossed on to a CBA/Ca background to ens ure Mtv-mediated deletion of V beta 11-expressing T cells in the resul tant offspring. Lymphomas arising from these mice were subsequently sc reened for V beta 11 expression. There was a clear correlation between the age at which mice developed neoplasia and the tumour phenotype. M ice with CD4(-) CD8(+) tumours succumbed to thymic lymphoma at a signi ficantly younger age than mice developing CD4(+) CD8(+) tumours. A sma ll number of tumours consisted of the 'forbidden' V beta 11 phenotype, showing that cells vulnerable to transformation could escape negative selection. The majority of the V beta 11-positive tumours were CD4(-) CD8(+) and were only observed in mice showing clinical evidence of tu mour development at a relatively young age. The phenotype of these cel ls and the age at which tumours arose suggests that T cells escaping t olerance may be susceptible to transformation.