Regulatory T cells (Tregs), including natural CD4+CD25+ Tregs and inducible IL-10 producing T regulatory type 1 (TR1) cells, maintain tolerance and inhibit autoimmunity. Recently, increased percentages of Tregs have been observed in the blood of septic patients, and ex vivo-activated Tregs were shown to prevent polymicrobial sepsis mortality. Whether endogenous Tregs contribute to sepsis outcome remains unclear. Polymicrobial sepsis, induced by cecal ligation and puncture, caused an increased number of splenic Tregs compared with sham-treated mice. Splenic CD4+CD25+ T cells from septic mice expressed higher levels of Foxp3 mRNA and were more efficient suppressors of CD4+CD25− T effector cell proliferation. Isolated CD4+ T cells from septic mice displayed increased intracellular IL-10 staining following stimulation, indicating that TR1 cells may also be elevated in sepsis. Surprisingly, Ab depletion of total CD4+ or CD4+CD25+ populations did not affect mortality. Furthermore, no difference in survival outcome was found between CD25 or IL-10 null mice and wild-type littermates, indicating that Treg or TR1-generated IL-10 are not required for survival. These results demonstrate that, although sepsis causes a relative increase in Treg number and increases their suppressive function, their presence does not contribute significantly to overall survival in this model.

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Type diabetes T D is an insulin-dependent diabetes because of insufficient insulin production by the pancreatic islet cells. "lthough the pathogenic mechanism of T D is not yetcompletely clear, the current view of T D pathogenesis is that under certain genetic background, exogenous and/or endogenous factors trigger autoimmunity against islet cells in the pancreas causing cell damage and subsequent insufficiency of insulin production [ , ]. "bout two decades ago, it was first demonstrated that T cells specific to cell antigens were activated and participated in the pathogenesis of T D [ , ]. " great deal of work following these reports in both animal models and humans has provided convincing data further supporting T D is a T cell-mediated autoimmune disease. On the other hand, the evidence showing that majority of T D patients have high titers of autoantibodies against islet cells [ , ] suggests that self-reactive " cells must also be involved in the autoimmune process. The role of " cells in the pathogenesis of T D was further supported by the recent research and clinical data demonstrating " cell depletion by anti-CD antibodies delayed the disease process.The clinical presentation of T D is preceded by a period of time of active autoimmune response occurring in the pancreatic islets. When overt diabetes occurs, approximately % of islets are destroyed. Therefore, tremendous efforts have been pulled in halting or slowing down autoimmune process for the purpose of preventing T D. Several clinical trials in T D prevention have been put forward. However, there is, thus far, no effective approach to the prevention of human T D despite that many have shown promising results in T D animal models. Further effort is needed to discover new ways to prevent T D. Importantly, from a practical point of view, reversing overt diabetes is much needed. In this chapter, we will fo- . Antibody-based therapies of type diabetesIn this section, we will discuss antibody-based therapy in T D including therapies using anti-CD and anti-CD antibodies as well as anti-thymocyte globulin. . . Anti-CD antibody therapy in type diabetes" cells are immune cells that produce antibodies when stimulated by exogenous or endogenous antigens. Several autoimmune diseases are associated with self-reactive " cells such as systemic lupus erythematosus and idiopathic thrombocytopenia. Reports have shown that depletion of " cells ameliorates such autoimmune conditions [ -]. CD is highly expressed on the surface of mature " cells and is the " cell-specific marker. Thus, anti-CD antibody has been employed for the in vivo depletion of " cells. The FD"-approved drug, anti-human CD , Rituximab has been used clinically for CD + " cell lymphoma for over a decade and largely improved the survival of patients with " cell lymphoma. Recently, anti-CD therapy was tested in several clinical trials for the treatment of " cell-mediated autoimmune diseases and demonstrated promising efficacy including a clinical study for the new onset T D patients [ ]. We will get into ...