B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets

Deepak Yadav, Valeria Judkowski, Malin Flodstrom-Tullberg, Lori Sterling, William L. Redmond, Linda Sherman, Nora Sarvetnick

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The B7-1/2-CD28 system provides the critical signal for the generation of an efficient T cell response. We investigated the role played by B7-2 in influencing pathogenic autoimmunity from islet-reactive CD4 T cells in B7-2 knockout (KO) NOD mice which are protected from type 1 diabetes. B7-2 deficiency caused a profound diminishment in the generation of spontaneously activated CD4 T cells and islet-specific CD4 T cell expansion. B7-2 does not impact the effector phase of the autoimmune response as adoptive transfer of islet Ag-specific BDC2.5 splenocytes stimulated in vitro could easily induce disease in B7-2KO mice. CD4 T cells showed some hallmarks of hyporesponsiveness because TCR/CD28-mediated stimulation led to defective activation and failure to induce disease in NODscid recipients. Furthermore, CD4 T cells exhibited enhanced death in the absence of B7-2. Interestingly, we found that B7-2 is required to achieve normal levels of CD4+CD25+CD62L+ T regulatory cells because a significant reduction of these T regulatory cells was observed in the thymus but not in the peripheral compartments of B7-2KO mice. In addition, our adoptive transfer experiments did not reveal either pathogenic or regulatory potential associated with the B7-2KO splenocytes. Finally, we found that the lack of B7-2 did not induce a compensatory increase in the B7-1 signal on APC in the PLN compartment. Taken together these results clearly indicate that B7-2 plays a critical role in priming islet-reactive CD4 T cells, suggesting a simplified, two-cell model for the impact of this costimulatory molecule in autoimmunity against islets.

Original languageEnglish (US)
Pages (from-to)3631-3639
Number of pages9
JournalJournal of Immunology
Volume173
Issue number6
DOIs
StatePublished - Sep 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yadav, D., Judkowski, V., Flodstrom-Tullberg, M., Sterling, L., Redmond, W. L., Sherman, L., & Sarvetnick, N. (2004). B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets. Journal of Immunology, 173(6), 3631-3639. https://doi.org/10.4049/jimmunol.173.6.3631