  We previously demonstrated that the abrogation of the ICOS pathway prevents
type 1 diabetes development in the Non Obese Diabetic (NOD) mouse, but results
in a CD4+ T-cell dependent autoimmune neuromyopathy in aged mice. Pancreatic
islet infiltrates in conventional NOD mice and neuromuscular infiltrates in
Icosl-/- NOD mice have in common that they exhibit a strong enrichment in
CD4+TIGIT+ T-cells, whilst TIGIT expression in the peripheral CD4+ T-cells is
limited to the CD4+FoxP3+ T-cell population.When deleting Tigit on the NOD
background, diabetes incidence was found increased. Peripheral CD4+CD226+
effector T-cells exhibited an increased frequency of IL-17 producing
CD4+CD226+RORgt+ T-cells versus a decreased frequency of IFN$\gamma$-producing
CD4+CD226+Tbet+ T-cells. ICOS is expressed in both CD4+FoxP3+ and CD4+CD226+
splenic T-cell subsets. Icosl deletion leads to a decrease of CD4+FoxP3+ cells,
with decrease of PD1 but increase of ICOS and CCRX3. Also in the Icosl-/-
model, CD4+CD226+ T-cells are decreased by Tigit deletion, and showed an
increase of CD4+CD226+RORgt+ T-cells and a decrease of CD4+CD226+Tbet+
T-cells.However, deletion of Tigit in aged Icosl-/- NOD mice population did not
increase the incidence of the autoimmune neuromyopathy observed in Icosl-/- NOD
mice. Interestingly, the upregulation of CD4+CD226+RORgt+ T-cells was partly
rescued.We conclude from our study that both Icosl and Tigit deletions on the
NOD background lead to a shift between the ratio of IFN$\gamma$ and
IL-17-producing CD4+CD226+ effector cells. The ICOS-dependent neuromyopathy
development remains dominant and is not further altered in the absence of
TIGIT.
