| First Author | Collin R | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 7 | Pages | 3503-12 |
| PubMed ID | 25165153 | Mgi Jnum | J:215148 |
| Mgi Id | MGI:5604724 | Doi | 10.4049/jimmunol.1400189 |
| Citation | Collin R, et al. (2014) The mouse idd2 locus is linked to the proportion of immunoregulatory double-negative T cells, a trait associated with autoimmune diabetes resistance. J Immunol 193(7):3503-12 |
| abstractText | Autoimmune diseases result from a break in immune tolerance. Various mechanisms of peripheral tolerance can protect against autoimmunity, including immunoregulatory CD4(-)CD8(-) double-negative (DN) T cells. Indeed, we have previously shown that diabetes-prone mouse strains exhibit a low proportion of DN T cells relative to that of diabetes-resistant mice, and that a single autologous transfer of DN T cells can impede autoimmune diabetes development, at least in the 3A9 TCR transgenic setting. In this study, we aim to understand the genetic basis for the difference in DN T cell proportion between diabetes-resistant and diabetes-prone mice. We thus perform an unbiased linkage analysis in 3A9 TCR F2 (NOD.H2(k) x B10.BR) mice and reveal that a locus on chromosome 9, which coincides with Idd2, is linked to the proportion of DN T cells in the lymph nodes. We generate two NOD.H2(k).B10-Chr9 congenic mouse strains and validate the role of this genetic interval in defining the proportion of DN T cells. Moreover, we find that the increased proportion of DN T cells in lymphoid organs is associated with a decrease in both diabetes incidence and serum IgG Ab levels. Together, the data suggest that Idd2 is linked to DN T cell proportion and that a physiological increase in DN T cell number may be sufficient to confer resistance to autoimmune diabetes. Altogether, these findings could help identify new candidate genes for the development of therapeutic avenues aimed at modulating DN T cell number for the prevention of autoimmune diseases. |
