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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1259-1268. Prepublished online as a Blood First Edition Paper on June 12, 2008; DOI 10.1182/blood-2007-12-130773. This Article Full Text (PDF) Supplemental Methods and Figure All Versions of this Article: blood-2007-12-130773v1 112/4/1259    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Huarte, E. Articles by Conejo-Garcia, J. R Search for Related Content PubMed PubMed Citation Articles by Huarte, E. Articles by Conejo-Garcia, J. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 27, 2007 Accepted May 13, 2008 PILAR is a novel modulator of human T cell expansion Eduardo Huarte, Juan R Cubillos-Ruiz, Yolanda C Nesbeth, Uciane K Scarlett, Diana G Martinez, Xavier A Engle, William F Rigby, Patricia A Pioli, Paul M Guyre, and Jose R Conejo-Garcia* Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH, United States Department of Medicine, Dartmouth Medical School, Lebanon, NH, United States Department of Physiology, Dartmouth Medical School, Lebanon, NH, United States * Corresponding author; email: jose.r.conejo-garcia{at}dartmouth.edu. Robust T cell responses without autoimmunity are only possible through a fine balance between activating and inhibitory signals. We have identified a novel modulator of T cell expansion, named Proliferation-Induced Lymphocyte-Associated Receptor (PILAR). Surface PILAR is markedly up-regulated on CD4 and, to a lesser extent, on CD8 T cells upon TCR engagement. In the absence of CD28 co-stimulation, PILAR signaling through CD161 supports CD3 antibody-dependent and antigen-specific T cell proliferation by increasing the expression of anti-apoptotic Bcl-xL and induces the secretion of Th1 cytokines. These effects are abrogated by PILAR blockade with specific antibodies, which decrease surface levels of CD28. In contrast, PILAR induces apoptotic death on naive and early activated T cells if CD161 engagement is blocked. PILAR is expressed by ~7-10% of CD4 T cells in two samples of inflammatory synovial fluid, suggesting a potential role in the pathogenesis of joint inflammation. Additionally, in the ovarian cancer microenvironment, effector T cells express PILAR, but not CD161, although the expression of both can be augmented ex vivo. Our results indicate that PILAR plays a central role in modulating the extent of T cell expansion. Manipulation of PILAR signaling may be important for the treatment of autoimmune diseases and cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Annunziato and S. Romagnani Do studies in humans better depict Th17 cells? Blood, September 10, 2009; 114(11): 2213 - 2219. [Abstract] [Full Text] [PDF] M. A. Kleinschek, K. Boniface, S. Sadekova, J. Grein, E. E. Murphy, S. P. Turner, L. Raskin, B. Desai, W. A. Faubion, R. de Waal Malefyt, et al. Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation J. Exp. Med., March 16, 2009; 206(3): 525 - 534. [Abstract] [Full Text] [PDF]

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