T Cells from NOD-PerIg Mice Target Both Pancreatic and Neuronal Tissue.
Document Type
Article
Publication Date
10-15-2020
Keywords
JMG, JAXCC
JAX Source
J Immunol 2020 Oct 15; 205(8):2026-2038
Volume
205
Issue
8
First Page
2026
Last Page
2038
ISSN
1550-6606
PMID
32938729
DOI
https://doi.org/10.4049/jimmunol.2000148
Grant
Juvenile Diabetes Research Foundation, DK46266,DK95735,NS054154,OD020351,CA034196
Abstract
The CD27-CD70 costimulatory pathway is essential for the full activation of T cells, but some studies show that blocking this pathway exacerbates certain autoimmune disorders. In this study, we report on the impact of CD27-CD70 signaling on disease progression in the NOD mouse model of type 1 diabetes (T1D). Specifically, our data demonstrate that CD70 ablation alters thymocyte selection and increases circulating T cell levels. CD27 signaling was particularly important for the thymic development and peripheral homeostasis of Foxp3+Helios+ regulatory T cells, which likely accounts for our finding that CD70-deficient NOD mice develop more-aggressive T1D onset. Interestingly, we found that CD27 signaling suppresses the thymic development and effector functions of T1D-protective invariant NKT cells. Thus, rather than providing costimulatory signals, the CD27-CD70 axis may represent a coinhibitory pathway for this immunoregulatory T cell population. Moreover, we showed that a CD27 agonist Ab reversed the effects of CD70 ablation, indicating that the phenotypes observed in CD70-deficient mice were likely due to a lack of CD27 signaling. Collectively, our results demonstrate that the CD27-CD70 costimulatory pathway regulates the differentiation program of multiple T cell subsets involved in T1D development and may be subject to therapeutic targeting.
Recommended Citation
Racine J,
Chapman H,
Doty RA,
Cairns B,
Hines T,
Tadenev A,
Anderson LC,
Green T,
Dyer M,
Wotton J,
Bichler Z,
White J,
Ettinger R,
Burgess RW,
Serreze DV.
T Cells from NOD-PerIg Mice Target Both Pancreatic and Neuronal Tissue. J Immunol 2020 Oct 15; 205(8):2026-2038