       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).

