11
Views
11
CrossRef citations to date
0
Altmetric
Original Article

Association of an Androgen-Responsive T Cell Phenotype with Murine Diabetes and Idd2

, , &
Pages 247-258 | Received 18 Apr 1995, Published online: 07 Jul 2009
 

Abstract

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] F, 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 egregated 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.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.