PT  - JOURNAL ARTICLE
AU  - Lepault, Françoise
AU  - Gagnerault, Marie Claude
TI  - Characterization of Peripheral Regulatory CD4<sup>+</sup> T Cells That Prevent Diabetes Onset in Nonobese Diabetic Mice
AID  - 10.4049/jimmunol.164.1.240
DP  - 2000 Jan 01
TA  - The Journal of Immunology
PG  - 240--247
VI  - 164
IP  - 1
4099  - http://www.jimmunol.org/content/164/1/240.short
4100  - http://www.jimmunol.org/content/164/1/240.full
SO  - J. Immunol.2000 Jan 01; 164
AB  - The period that precedes onset of insulin-dependent diabetes mellitus corresponds to an active dynamic state in which pathogenic autoreactive T cells are kept from destroying β cells by regulatory T cells. In prediabetic nonobese diabetic (NOD) mice, CD4+ splenocytes were shown to prevent diabetes transfer in immunodeficient NOD recipients. We now demonstrate that regulatory splenocytes belong to the CD4+ CD62Lhigh T cell subset that comprises a vast majority of naive cells producing low levels of IL-2 and IFN-γ and no IL-4 and IL-10 upon in vitro stimulation. Consistently, the inhibition of diabetes transfer was not mediated by IL-4 and IL-10. Regulatory cells homed to the pancreas and modified the migration of diabetogenic to the islets, which resulted in a decreased insulitis severity. The efficiency of CD62L+ T cells was dose dependent, independent of sex and disease prevalence. Protection mechanisms did not involve the CD62L molecule, an observation that may relate to the fact that CD4+ CD62Lhigh lymph node cells were less potent than their splenic counterparts. Regulatory T cells were detectable after weaning and persist until disease onset, sustaining the notion that diabetes is a late and abrupt event. Thus, the CD62L molecule appears as a unique marker that can discriminate diabetogenic (previously shown to be CD62L−) from regulatory T cells. The phenotypic and functional characteristics of protective CD4+ CD62L+ cells suggest they are different from Th2-, Tr1-, and NK T-type cells, reported to be implicated in the control of diabetes in NOD mice, and may represent a new immunoregulatory population.