Autoimmunity during thymectomy-induced lymphopenia: role of thymus ablation and initial effector T cell activation timing in nonobese diabetic mice.
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.
INSERM Unité 561, René Descartes University, Saint-Vincent-de-Paul Hospital, Paris, France.
Marie-Claude
MC
Gagnerault
Olivia
O
Lanvin
Virginie
V
Pasquier
Corinne
C
Garcia
Diane
D
Damotte
Bruno
B
Lucas
Françoise
F
Lepault
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005756:Gastritis / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology* / Q000601:surgery