B7-1 mediated costimulation regulates pancreatic autoimmunity

Deepak Yadav, Cody Fine, Miyuki Azuma, Nora E Sarvetnick

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Costimulation by B7-1 and B7-2 molecules results in divergent biological effects. This is particularly striking in the NOD mouse, since the lack of B7-2 leads to complete protection from diabetes whereas the B7-1 deficiency causes exacerbation of disease. We tested the hypothesis that B7-1 costimulation suppresses pancreatic autoimmunity. We describe that the lack of B7-1 not only causes aberrant thymocyte maturation but also significantly enhances expansion, survival, and effector function of islet specific T cells in periphery. We also observed a significant reduction in the proportion of T-regulatory (T-regs) cells. Immunophenotypic analysis of T and APCs revealed a significantly lower frequency of T cells expressing the negative costimulatory receptor PD-1 in B7-1KO mice whereas the proportion of B7-H1 positive APCs was found to be significantly higher. Blocking studies in B7-1KO mice suggest that B7-H1 provides negative signals for anti islet CD4 and CD8 T-cell expansion but is differentially required for their priming. Our data demonstrate that deficiency of B7-1 mediated costimulation causes multitude of immunological defects, which involve reduction in T-regs and a concomitant enhancement of expansion, survival and effector potential of auto reactive T cells.

Original languageEnglish (US)
Pages (from-to)2616-2624
Number of pages9
JournalMolecular Immunology
Volume44
Issue number10
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

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Autoimmunity
T-Lymphocytes
Programmed Cell Death 1 Receptor
B7 Antigens
Inbred NOD Mouse
Regulatory T-Lymphocytes
Thymocytes
Disease Progression

Keywords

  • Autoimmunity
  • B7-1
  • Costimulation
  • NOD
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

B7-1 mediated costimulation regulates pancreatic autoimmunity. / Yadav, Deepak; Fine, Cody; Azuma, Miyuki; Sarvetnick, Nora E.

In: Molecular Immunology, Vol. 44, No. 10, 01.04.2007, p. 2616-2624.

Research output: Contribution to journalArticle

Yadav, Deepak ; Fine, Cody ; Azuma, Miyuki ; Sarvetnick, Nora E. / B7-1 mediated costimulation regulates pancreatic autoimmunity. In: Molecular Immunology. 2007 ; Vol. 44, No. 10. pp. 2616-2624.
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