Normal individuals co-exist with vast numbers of commensal microflora in their mucosal tissues without any pathological problems. Abnormality in the establishment or maintenance of such symbiotic relationship can lead to chronic immune responses towards the commensal microflora, and the responses in the gastrointestinal tract can lead to the development of inflammatory bowl diseases (IBD), such as Crohn's disease and ulcerative colitis. A widely used animal model to study IBD is the system of adoptively transferring naive CD4 T cells into syngeneic immunodeficient hosts, which leads to chronic inflammation in the intestines from unregulated T cell responses to enteric commensal microflora antigens. While the disease in this system is efficiently blocked by co-transfer of regulatory T cells (Tregs), the reasons why commensal bacterial antigens become overtly immunogenic in the first place is far from clear. To better understand this issue, the following two areas of investigation are proposed: First, the presence of a novel population of T cells with the ability to regulate enteric antigen presentation will be sought using a strain of severely lymphopenic mice that is resistant to IBD induction. Second, the presence of a population of T cells that can regulate enteric antigen presentation in normal mice will be sought using the information gained from the lymphopenic mice. The results from these studies may be useful in better understanding the etiology of IBD in humans and in the development of new therapeutic approaches for treatment of the disease.
Inflammatory bowel disease (IBD) is a debilitating chronic disease affecting the intestines from unknown causes. This proposal is designed to define the basis for the early events leading to IBD in a mouse model of human IBD. The findings from this proposal may be useful in better understanding the etiology of human IBD and in the development of new therapeutic approaches for treatment of the human disease.
|Carrette, Florent; Surh, Charles D (2012) IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis. Semin Immunol 24:209-17|
|Sprent, Jonathan; Surh, Charles D (2011) Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells. Nat Immunol 12:478-84|
|Loewendorf, Andrea I; Arens, Ramon; Purton, Jared F et al. (2011) Dissecting the requirements for maintenance of the CMV-specific memory T-cell pool. Viral Immunol 24:351-5|
|Letourneau, Sven; van Leeuwen, Ester M M; Krieg, Carsten et al. (2010) IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25. Proc Natl Acad Sci U S A 107:2171-6|
|Surh, Charles D; Sprent, Jonathan (2010) Glimpsing the real CD4+ T cell response. Nat Immunol 11:47-9|
|Sprent, Jonathan; Surh, Charles D (2009) Re-entry of mature T cells to the thymus: an epiphenomenon? Immunol Cell Biol 87:46-9|