MAIT cell alterations in adults with recent-onset and long-t
Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes expressing an AlphaBeta T cell antigen receptor that recognizes the MHC-related 1 molecule. MAIT cells are altered in children at risk for and with type 1 diabetes, and mouse model studies have shown MAIT cell involvement in type 1 diabetes development. Since several studies support heterogeneity in type 1 diabetes physiopathology according to the age of individuals, we investigated whether MAIT cells were altered in adults with type 1 diabetes.

MAIT cell frequency, phenotype and function were analyzed by flow cytometry, using fresh peripheral blood from 21 adults with recent-onset type 1 diabetes (2–14 days after disease onset) and 47 adults with long-term disease (more than 2 years after diagnosis) compared with 55 healthy blood donors. Researchers also separately analyzed 17 women with long-term type 1 diabetes and an associated autoimmune disease, compared with 30 healthy women and 27 women with long-term type 1 diabetes.

Results:
-- MAIT cells from adults with recent-onset type 1 diabetes, compared with healthy adult donors, harboured a strongly activated phenotype indicated by an elevated CD25+ MAIT cell frequency.

-- In adults with long-term type 1 diabetes, MAIT cells displayed an activated and exhausted phenotype characterized by high CD25 and programmed cell death 1 (PD1) expression and a decreased production of proinflammatory cytokines, IL-2, IFN-Gamma and TNF-alpha.

-- Even though MAIT cells from these patients showed upregulated IL-17 and IL-4 production, the polyfunctionality of MAIT cells was decreased and the frequency of MAIT cells producing none of the effector molecules analyzed increased (median 34.40 vs 19.30% of MAIT cells).

-- Several MAIT cell variables correlated with HbA1c level and more particularly in patients with recent-onset type 1 diabetes. In women with long-term type 1 diabetes, MAIT cell alterations were more pronounced in those with an associated autoimmune disease than in those without another autoimmune disease.

-- In women with long-term type 1 diabetes and an associated autoimmune disease, there was an increase in CD69 expression and a decrease in the survival B-cell lymphoma 2 (BCL-2) and CD127 (IL-7R) marker expression compared with women without a concomitant autoimmune disorder.

-- Concerning effector molecules, TNF-alpha and granzyme B production by MAIT cells was decreased.

Conclusively, alterations in MAIT cell frequency, phenotype and function were more pronounced in adults with long-term type 1 diabetes compared with adults with recent-onset type 1 diabetes. There were several correlations between MAIT cell variables and clinical characteristics. Moreover, the presence of another autoimmune disease in women with long-term type 1 diabetes further exacerbated MAIT cell alterations. These results suggest that MAIT cell alterations in adults with type 1 diabetes could be associated with two aspects of the disease: impaired glucose homeostasis; and autoimmunity.

Source: https://link.springer.com/article/10.1007/s00125-021-05527-y
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