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

27 Citations (Scopus)

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

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Islets of Langerhans
T-Lymphocytes
Autoimmunity
Adoptive Transfer
Regulatory T-Lymphocytes
Inbred NOD Mouse
Type 1 Diabetes Mellitus
Knockout Mice
Thymus Gland

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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

B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets. / Yadav, Deepak; Judkowski, Valeria; Flodstrom-Tullberg, Malin; Sterling, Lori; Redmond, William L.; Sherman, Linda; Sarvetnick, Nora.

In: Journal of Immunology, Vol. 173, No. 6, 15.09.2004, p. 3631-3639.

Research output: Contribution to journalArticle

Yadav, D, Judkowski, V, Flodstrom-Tullberg, M, Sterling, L, Redmond, WL, Sherman, L & Sarvetnick, N 2004, 'B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets', Journal of Immunology, vol. 173, no. 6, pp. 3631-3639. https://doi.org/10.4049/jimmunol.173.6.3631
Yadav D, Judkowski V, Flodstrom-Tullberg M, Sterling L, Redmond WL, Sherman L et al. B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets. Journal of Immunology. 2004 Sep 15;173(6):3631-3639. https://doi.org/10.4049/jimmunol.173.6.3631
Yadav, Deepak ; Judkowski, Valeria ; Flodstrom-Tullberg, Malin ; Sterling, Lori ; Redmond, William L. ; Sherman, Linda ; Sarvetnick, Nora. / B7-2 (CD86) controls the priming of autoreactive CD4 T cell response against pancreatic islets. In: Journal of Immunology. 2004 ; Vol. 173, No. 6. pp. 3631-3639.
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