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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 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 Citation Map 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. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY PILAR is a novel modulator of human T-cell expansion Eduardo Huarte1,*, Juan R. Cubillos-Ruiz1,*, Yolanda C. Nesbeth1,*, Uciane K. Scarlett1, Diana G. Martinez1, Xavier A. Engle1, William F. Rigby1,2, Patricia A. Pioli3, Paul M. Guyre1,3, and Jose R. Conejo-Garcia1,2 Departments of1 Microbiology and Immunology, 2 Medicine, and 3 Physiology, Dartmouth Medical School, Lebanon, NH 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 on T-cell receptor engagement. In absence of CD28 costimulation, PILAR signaling through CD161 supports CD3 antibody-dependent and antigen-specificT-cell proliferation by increasing the expression of antiapoptotic Bcl-xL and induces secretion of T helper type 1 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 approximately 7% to 10% of CD4 T cells in 2 samples of inflammatory synovial fluid, suggesting a potential role in the pathogenesis of joint inflammation. In addition, in the ovarian cancer microenvironment, effector T cells express PILAR, but not CD161, although 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 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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