http://intimm.oxfordjournals.org International Immunology - RSS feed of articles 1460-2377 International Immunology 0953-8178 http://intimm.oxfordjournals.org/cgi/content/short/dxp107v1?rss=1 Chronic viral infections are often characterized by CD8 T-cell responses with poor cytokine secretion potential and limited expansion of the CD8 T-cell pool, collectively referred to as CD8 T-cell exhaustion. Exhaustion of lymphocytic choriomeningitis virus (LCMV)-specific CD8 T cells was shown to be partially regulated by the inhibitory receptor programmed death 1 (PD-1). Here, we demonstrate that exhausted LCMV-specific CD8 T cells also express the negative regulatory receptor lymphocyte activation gene 3 (LAG-3) which is mainly expressed on cells co-expressing the negative regulatory receptors PD-1 and Tim-3. Expression levels of LAG-3 on anti-viral CD8 T cells remain stable over short-term in vitro stimulations in presence of antigenic peptide. Nevertheless, in vitro and in vivo blockade of LAG-3 did not rescue cytokine production by virus-specific CD8 T cells and did not alter the virus titer in various organs. Likewise, chronic LCMV infection of LAG-3–/– mice led to a comparable degree of T-cell exhaustion as observed in C57BL/6 controls and to similar virus titers. Further, LAG-3 did not influence T-cell activation or cell division during chronic LCMV infection. These data suggest that even though LAG-3 is continuously up-regulated on LCMV-specific exhausted CD8 T cells, it alone does not significantly contribute to T-cell exhaustion.

]]> Fri, 30 Oct 2009 07:42:40 PDT info:doi/10.1093/intimm/dxp107 The Japanese Society for Immunology 2009-10-30 Article http://intimm.oxfordjournals.org/cgi/content/short/dxp104v2?rss=1 Invariant NKT (iNKT) cells bridge innate and acquired immunity and play an important role in both protective and regulatory responses. The nature of the response is dictated by the initial cytokine environment: interaction with IL-10-producing cells induces negative regulatory T_h2/regulatory T cell-type iNKT cells, while that with IL-12-producing cells results in pro-inflammatory T_h1-type responses. Particularly, in the anti-tumor response, iNKT cells mediate adjuvant activity by their production of IFN-, which in turn activates both innate and acquired immune systems. Thus, upon activation of iNKT cells, both MHC^– and MHC⁺ tumor cells can be efficiently eliminated. On the basis of these mechanisms, iNKT cell-targeted adjuvant cell therapies have been developed and have shown great promise in initial clinical trials on cancer patients.

]]> Tue, 27 Oct 2009 06:03:05 PDT info:doi/10.1093/intimm/dxp104 The Japanese Society for Immunology 2009-10-27 Review