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. 1996 Jan;73(1):13–17. doi: 10.1038/bjc.1996.3

Apparent bypass of negative selection in CD8+ tumours in CD2-myc transgenic mice.

E R Cameron 1, M Campbell 1, K Blyth 1, S A Argyle 1, L Keanie 1, J C Neil 1, D E Onions 1
PMCID: PMC2074291  PMID: 8554976

Abstract

A role for antigen stimulation in lymphoid neoplasia has been postulated and is supported by indirect evidence that suggests that the interaction of antigen with both T cells and B cells may constitute an epigenetic event that can contribute to tumour induction or tumour progression. Using myc-bearing transgenic mice that develop mainly clonal T-cell lymphomas we have investigated the possibility that endogenous antigen-mediated clonal deletion might be overridden in tumorigenesis. CD2-myc transgenic mice were backcrossed on to a CBA/Ca background to ensure Mtv-mediated deletion of V beta 11-expressing T cells in the resultant offspring. Lymphomas arising from these mice were subsequently screened for V beta 11 expression. There was a clear correlation between the age at which mice developed neoplasia and the tumour phenotype. Mice with CD4- CD8+ tumours succumbed to thymic lymphoma at a significantly younger age than mice developing CD4+ CD8+ tumours. A small 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 tumour development at a relatively young age. The phenotype of these cells and the age at which tumours arose suggests that T cells escaping tolerance may be susceptible to transformation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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