Apparent bypass of negative selection in CD8+ tumours in CD2-myc transgenic mice.
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.
Cameron
E R
ER
Department of Veterinary Pathology, University of Glasgow Veterinary School, UK.
Campbell
M
M
Blyth
K
K
Argyle
S A
SA
Keanie
L
L
Neil
J C
JC
Onions
D E
DE
D000818:Animals; D018801:CD2 Antigens / Q000235:genetics*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D016259:Genes, myc; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D018089:Superantigens / Q000276:immunology
D018801:CD2 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens