BTLA targeting modulates lymphocyte phenotype, function, and numbers and attenuates disease in nonobese diabetic mice

Wayne Truong, Wayne W. Hancock, Jennifer C. Plester, Shaheed Merani, David C. Rayner, Govindarajan Thangavelu, Kenneth M. Murphy, Colin C. Anderson, A. M.James Shapiro

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The novel coinhibitory receptor BTLA may have a regulatory role in maintaining peripheral tolerance; however, its role in autoimmune diabetes is unknown. In this study, we show that anti-BTLA mAb 6F7 selectively depleted pathogenic B and CD4+ TH cells; enhanced the proportion of cells with the forkhead box p3+ PD-1+CD4+ regulatory T phenotype; and increased the production of potentially protective (IL-10) and detrimental (IL-2, IFN-γ) cytokines in NOD mice. As interactions between BTLA and PD-1 coinhibitory pathways have been described in the cardiac allograft model, we also investigated if these pathways may have significant interaction in autoimmune diabetes. Anti-BTLA inhibited anti-PD-1-potentiated total IL-12 (p40+p70) production, suggesting the possibility that anti-BTLA may have a greater effect in the setting of anti-PD-1-triggered diabetes. To test this, NOD mice at 4 and 10 weeks of age were treated with anti-BTLA mAb, anti-PD-1 mAb, both mAb, or isotype control and were monitored for diabetes development. Although anti-BTLA mAb delayed diabetes onset significantly in 10- but not 4-week-old NOD mice, anti-BTLA mAb attenuated anti-PD-1-induced diabetes in both age groups. Hence, strategies targeting BTLA+ lymphocytes or therapies enhancing the BTLA-negative cosignal may prove valuable in treating autoimmune diabetes.

Original languageEnglish (US)
Pages (from-to)41-51
Number of pages11
JournalJournal of Leukocyte Biology
Issue number1
StatePublished - Jul 1 2009
Externally publishedYes


  • Coinhibitory receptors
  • Cytokines
  • Depletion
  • Diabetes mellitus
  • Monoclonal antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


Dive into the research topics of 'BTLA targeting modulates lymphocyte phenotype, function, and numbers and attenuates disease in nonobese diabetic mice'. Together they form a unique fingerprint.

Cite this