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M9650535.TXT
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1996-03-09
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Document 0535
DOCN M9650535
TI Apparent bypass of negative selection in CD8+ tumours in CD2-myc
transgenic mice.
DT 9605
AU Cameron ER; Campbell M; Blyth K; Argyle SA; Keanie L; Neil JC; Onions
DE; Department of Veterinary Pathology, University of Glasgow;
Veterinary School, UK.
SO Br J Cancer. 1996 Jan;73(1):13-7. Unique Identifier : AIDSLINE
MED/96146594
AB 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.
DE Animal Antigens, CD2/*GENETICS Cell Transformation,
Neoplastic/*IMMUNOLOGY CD4-CD8 Ratio CD4-Positive
T-Lymphocytes/IMMUNOLOGY CD8-Positive
T-Lymphocytes/*IMMUNOLOGY/PATHOLOGY *Genes, myc Lymphoma,
T-Cell/GENETICS/*IMMUNOLOGY/PATHOLOGY Mice Mice, Inbred CBA Mice,
Inbred C57BL Mice, Transgenic Phenotype Receptors, Antigen, T-Cell,
alpha-beta/GENETICS/IMMUNOLOGY Superantigens/IMMUNOLOGY Support,
Non-U.S. Gov't JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).