- The chronic GVH reaction is induced in inbred strains of mice by a transfer of spleen and lymph node T cells that recognize a foreign MHC class II determinant in the recipient. This syndrome is characterized by a spectrum of autoantibodies and immunopathological changes that closely parallels those found in human systemic lupus erythematosus. Previous work by the principal investigator's laboratory and others have shown that this disease is induced by the donor alloreactive T cells that recognize foreign MHC class II on B cells of the recipient that are in turn, induced to produce autoantibodies. In the current application, the principal investigator proposes to study the specific role of the donor and recipient T cells as well as the recipient B cells in chronic GVH.
His specific aims are (1) To learn how B cell tolerance is lost in the chronic GVH reaction; (2) to understand what the role is of endogenous T cells in the chronic GVH response; and, (3) to determine what the role is of donor T cells in the chronic GVH response. These studies, the applicants expect, will provide important insight into the mechanism of autoantibody production and loss of tolerance in the chronic GVH response. This, they believe, will help in understanding the underlying mechanisms that produce the loss of tolerance characteristic of spontaneous systemic lupus erythematosus (SLE), both in mice and in humans. Such understanding will, eventually, lead to more rational therapy for this disease and other autoimmune diseases.
Cheng, Tao; Choi, Yongwon; Finkel, Terri H et al. (2013) Tumor necrosis factor receptor-associated factor 1 influences KRN/I-Ag7 mouse arthritis autoantibody production. J Clin Immunol 33:759-66 |
Eisenberg, Robert A; Jawad, Abbas F; Boyer, Jean et al. (2013) Rituximab-treated patients have a poor response to influenza vaccination. J Clin Immunol 33:388-96 |
Meng, Wenzhao; Li, Yongmei; Xue, Emily et al. (2012) B-cell tolerance defects in the B6.Aec1/2 mouse model of Sjögren's syndrome. J Clin Immunol 32:551-64 |
Eisenberg, Robert A (2012) Secondary receptor editing in the generation of autoimmunity. Autoimmun Rev 11:787-9 |
Miwa, Takashi; Zhou, Lin; Maldonado, Michael A et al. (2012) Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice. J Immunol 189:5434-41 |
Eisenberg, Robert A; Via, Charles S (2012) T cells, murine chronic graft-versus-host disease and autoimmunity. J Autoimmun 39:240-7 |
Garchow, Barry G; Bartulos Encinas, Oscar; Leung, Yiu Tak et al. (2011) Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice. EMBO Mol Med 3:605-15 |
Meng, Wenzhao; Yunk, Lenka; Wang, Li-San et al. (2011) Selection of individual VH genes occurs at the pro-B to pre-B cell transition. J Immunol 187:1835-44 |
Luning Prak, Eline T; Monestier, Marc; Eisenberg, Robert A (2011) B cell receptor editing in tolerance and autoimmunity. Ann N Y Acad Sci 1217:96-121 |
Tsao, Patricia Y; Arora, Vaishali; Ji, Mei Qing et al. (2011) KRN/I-Ag7 mouse arthritis is independent of complement C3. J Clin Immunol 31:857-63 |
Showing the most recent 10 out of 59 publications