title: Spontaneous proliferation of H2M-/- CD4 T cells results in unusual acute hepatocellular necrosis.
abstract: Naïve CD4 T cells are triggered to undergo spontaneous proliferation, a proliferative response induced in response to homeostatic stimulation, when exposed to severe lymphopenic environments. They spontaneously acquire proinflammatory effector phenotypes, playing a major role in inducing chronic inflammation in the intestine that is believed to be induced by T cell recognition of commensal antigens. While the antigens inducing the T cell responses and inflammation are being extensively investigated, the role of clonality of T cells involved in this process remains poorly understood. In this study, we utilized naïve CD4 T cells isolated from B6 H2M-/- mice, in which MHCII molecules are complexed with a single CLIP molecule, and examined spontaneous proliferation and intestinal inflammation of CD4 T cells expressing limited T cell receptor repertoire diversity. We found that H2M-/- CD4 T cells undergo robust spontaneous proliferation, differentiate into IFNγ-producing Th1 type effector cells, and, most unexpectedly, induce severe acute hepatocellular necrosis. T cell interaction with MHCII molecule on cells of hematopoietic origin was essential to induce the pathology. Interestingly, B cells are fully capable of preventing necrotic inflammation via IL-10-independent and B7-H1-dependent mechanism. This could be a useful animal model to examine T cell-mediated liver inflammation and B cell-mediated immune regulation.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.
authors.forename: Jeong-su
authors.initials: JS
authors.lastname: Do
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.
authors.forename: William M
authors.initials: WM
authors.lastname: Baldwin
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.
authors.forename: Booki
authors.initials: B
authors.lastname: Min
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006183:H-2 Antigens / Q000235:genetics*; D006505:Hepatitis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D009336:Necrosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D060890:B7-H1 Antigen; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; C045084:invariant chain; D007371:Interferon-gamma