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1996-02-26
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Document 0952
DOCN M9620952
TI Association of an androgen-responsive T cell phenotype with murine
diabetes and Idd2.
DT 9602
AU Pearce RB; Formby B; Healy K; Peterson CM; Sansum Medical Research
Foundation, Santa Barbara, CA 93105, USA.
SO Autoimmunity. 1995;20(4):247-58. Unique Identifier : AIDSLINE
MED/96048134
AB T cells are involved in the induction and suppression of autoimmune
diabetes in nonobese diabetic (NOD) mice. Because the incidence of
diabetes is 13-fold greater in NOD/Smrf females, we searched for T cell
phenotypes that showed sexual dimorphism and associated with diabetes in
backcross segregants. The percentage of CD4+PBL was higher in NOD/Smrf
females than males, was intermediate in [NOD X NON] F1 mice and
approximated a 1:1 distribution in F1 mice backcrossed to either NOD or
NON parental strains, suggesting primary control of the phenotype by an
incompletely dominant gene, but not excluding additional effects by
other genes. We term this primary gene Tlf(T lymphocyte frequency)
because it also influenced the percentage of CD8+ T cells, although to
lesser extent and independently from the MHC previously shown to lower
the CD8+ T cell fraction in NON mice. Tlf segregated with diabetes in
BC1 females, suggesting linkage with at least one diabetic locus.
Genotyping of markers for Idd1, Idd2, and Idd3/10 revealed that Tlf
mapped with Idd2 on chromosome 9. Dihydrotestosterone simultaneously
lowered CD4+ PBL levels and prevented diabetes in NOD females while, in
vitro, it had a differential effect on Con A elicited cytokines,
increasing IL-2 22% and decreasing IL-4 39% (p < 0.0001). Thus the Tlf
phenotype in NOD females, like diabetes, can be modulated by androgens.
DE Animal Base Sequence CD4-Positive T-Lymphocytes/IMMUNOLOGY
CD8-Positive T-Lymphocytes/IMMUNOLOGY Diabetes Mellitus,
Insulin-Dependent/*GENETICS/*IMMUNOLOGY Female
Interleukin-2/BIOSYNTHESIS Linkage (Genetics) Male Mice Mice, Inbred
NOD Molecular Sequence Data Phenotype Stanolone/*PHARMACOLOGY
Support, Non-U.S. Gov't T-Lymphocytes/*IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).