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

Cameron, E.R. , Campbell, M., Blyth, K. , Argyle, S.A., Keanie, L., Neil, J.C. and Onions, D.E. (1996) Apparent bypass of negative selection in CD8+ tumours in CD2-myc transgenic mice. British Journal of Cancer, 73(1), pp. 13-17. (doi: 10.1038/bjc.1996.3) (PMID:8554976) (PMCID:PMC2074291)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Onions, Professor David and Neil, Professor James and Argyle, Dr Sally and Blyth, Professor Karen and Cameron, Professor Ewan
• Authors: Cameron, E.R., Campbell, M., Blyth, K., Argyle, S.A., Keanie, L., Neil, J.C., and Onions, D.E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: British Journal of Cancer
• Publisher: Nature Publishing Group
• ISSN: 0007-0920