Autoimmunity during thymectomy-induced lymphopenia: role of thymus ablation and initial effector T cell activation timing in nonobese diabetic mice.
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| Abstract |
Autoimmune diseases develop in selected normal mouse strains when thymectomy (Tx) is performed at 3 days of age (d3-Tx). Insufficient T cell regulation after Tx may result from a defect in regulatory T (Treg) cells or from an augmented effector T (Teff) cell number/pathogenicity. We have previously shown that Tx at 3 wk (wk3-Tx), the age of massive islet Ag release, accelerates diabetes onset. We now have determined diabetes incidence in d3-Tx nonobese diabetic mice and compared the frequency and function of their Teff and Treg cells with those of wk3-Tx mice. We found that d3-Tx had no effect on diabetes incidence, but induced gastritis. After day 3 and week 3 Tx, Treg cells were fully competent and their frequency increased. The number of diabetogenic T cells was greatly amplified after wk3-Tx and likely overcame Treg cell control, leading to an early tolerance breakdown. By contrast, in d3-Tx mice, activation concerned few cells and Teff cell amplification remained controlled. This suggests that Tx enhances autoimmunity when it coincides with the first encounter of autoreactive T cells with their cognate Ag. The relationship between Tx-induced lymphopenia, tissue remodeling, and autoimmunity is discussed.
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| Authors | Marie-Claude Gagnerault, Olivia Lanvin, Virginie Pasquier, Corinne Garcia, Diane Damotte, Bruno Lucas, Françoise Lepault |
| Journal | Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 8 Pg. 4913-20 (Oct 15 2009) ISSN: 1550-6606 [Electronic] United States |
| PMID | 19801516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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