Intrinsic Differences in Donor CD4 T Cell IL-2 Production Influence Severity of Parent-into-F1 Murine Lupus by Skewing the Immune Response Either toward Help for B Cells and a Sustained Autoantibody Response or toward Help for CD8 T Cells and a Downregulatory Th1 Response

The Journal of Immunology : Official Journal of the American Association of Immunologists
Kateryna SoloviovaCharles S Via

Abstract

Using the parent-into-F1 model of induced lupus and (C57BL/6 × DBA2) F1 mice as hosts, we compared the inherent lupus-inducing properties of the two parental strain CD4 T cells. To control for donor CD4 recognition of alloantigen, we used H-2(d) identical DBA/2 and B10.D2 donor T cells. We demonstrate that these two normal, nonlupus-prone parental strains exhibit two different T cell activation pathways in vivo. B10.D2 CD4 T cells induce a strong Th1/CMI pathway that is characterized by IL-2/IFN-γ expression, help for CD8 CTLs, and skewing of dendritic cell (DC) subsets toward CD8a DCs, coupled with reduced CD4 T follicular helper cells and transient B cell help. In contrast, DBA/2 CD4 T cells exhibit a reciprocal, lupus-inducing pathway that is characterized by poor IL-2/IFN-γ expression, poor help for CD8 CTLs, and skewing of DC subsets toward plasmacytoid DCs, coupled with greater CD4 T follicular helper cells, prolonged B cell activation, autoantibody formation, and lupus-like renal disease. Additionally, two distinct in vivo splenic gene-expression signatures were induced. In vitro analysis of TCR signaling revealed defective DBA CD4 T cell induction of NF-κB, reduced degradation of IκBα, and increased expression of the NF...Continue Reading

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Citations

Apr 1, 2017·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Charles S ViaFred D Finkelman
Oct 28, 2019·Biogerontology·Zorica Stojić-VukanićGordana Leposavić
Jun 26, 2018·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Kateryna SoloviovaCharles S Via
Apr 9, 2021·Cellular Immunology·Rajkumar VenkatadriRahul Sharma

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