Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation
Susumu Ikehara,H Ohtsuki,Robert A. Good,H Asamoto,Nakamura T,Kenichi Sekita,Eri Muso,Y Tochino,T Ida,H Kuzuya +9 more
Reads0
Chats0
TLDR
The results suggest that bone marrow transplantation may ultimately be developed as a component of a strategy to be employed for treatment of type I diabetes in humans.Abstract:
An animal model [the nonobese diabetic (NOD) mouse] for type I diabetes features a striking infiltration of T cells into the pancreatic islets This infiltration selectively destroys beta cells Most of the T cells are Lyt-1+, but some are Lyt-2+,3+ Transfer experiments using parabiosis revealed that insulitis can be transferred within 2 weeks after parabiosis to immunoincompetent thymectomized mice When NOD mice (6 mo old) were irradiated and reconstituted with bone marrow cells from young BALB/c nu/nu mice (less than 2 mo old), the NOD mice exhibited neither insulitis nor overt diabetes Deposits of immunoglobulin in mesangial areas of the glomeruli disappeared within 3 mo after bone marrow transplantation in such irradiated allogeneic bone marrow reconstituted mice Assays for immunological functions, including mitogen response and mixed lymphocyte reaction, revealed that both T- and B-cell functions were increased in NOD mice with overt diabetes NOD mice reconstituted with BALB/c nu/nu bone marrow cells displayed normal T- and B-cell functions The newly developed T cells in the allogeneic bone marrow recipients are tolerant to cells with both donor- and host-type major histocompatibility complex determinants These results suggest that bone marrow transplantation may ultimately be developed as a component of a strategy to be employed for treatment of type I diabetes in humansread more
Citations
More filters
Journal ArticleDOI
Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells.
TL;DR: The neonatal syngeneic transfer provides an effective model for studies of the cellular events involved at regulatory and effector stages of autoimmune type I diabetes.
Journal ArticleDOI
Prevention of Type I Diabetes in NOD Mice by Adjuvant Immunotherapy
TL;DR: The results suggest that early nonspecific immunotherapy of genetically predisposed individuals could prevent the development of autoimmune diabetes and lend support to a relationship between the boosting of endogenous NS activity and the establishment of tolerance to self in the context of autoimmunity.
Journal ArticleDOI
T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice.
TL;DR: Findings indicate that suppressive CD4+ T cells that are dependent on the presence of the thymus may delay the onset of diabetes in female diabetes-prone NOD mice.
Journal ArticleDOI
Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice.
Taketoshi Kushida,Muneo Inaba,Hiroko Hisha,Naoya Ichioka,Takashi Esumi,Ryokei Ogawa,Hirokazu Iida,Susumu Ikehara +7 more
TL;DR: It is shown that a new bone marrow transplantation method consisting of fractionated irradiation, followed by intra-bone marrow (IBM) injection of whole bone marrow cells from allogeneic normal C57BL/6 (B6) mice, resulting in the complete amelioration of intractable autoimmune diseases in chimeric resistant MRL/lpr mice without recourse to immunosuppressants is suitable for human therapy.
References
More filters
Journal ArticleDOI
Pathologic Anatomy of the Pancreas in Juvenile Diabetes Mellitus
TL;DR: Quantitative study of insular tissue has revealed that the number of B cells is greatly diminished in Patients with acute juvenile diabetes from the time of clinical onset of the disease, and may be assumed that during the preclinical phase of juvenile diabetes, an extrapancreatic factor has exerted a strong stimulant action on theinsular tissue.
Journal ArticleDOI
Simultaneous localization of multiple tissue antigens using the peroxidase-labeled antibody method: a study on pituitary glands of the rat.
TL;DR: The peroxidase-labeled antibody method was modified to localize multiple tissue antigens in a single histologic section, using substrates that develop reaction products of different colors to identify the antigenic sites.
Journal ArticleDOI
The Spontaneously Diabetic Wistar Rat: Metabolic and Morphologic Studies
TL;DR: This model of spontaneous diabetes in nonobese rats displays insulin deficiency, glucagon excess, and ketosis, with a dramatic inflammatory lesion during active β-cell destruction, in relation to the severity of the syndrome.
Journal ArticleDOI
Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer
TL;DR: Adoptive transfer experiments in both systems revealed that the destruction of ovaries in postthymectomy autoimmune oophoritis was mediated by Lyt-1 T cells, suggesting that the effector mechanisms may be closely related to a DTH reaction.
Journal ArticleDOI
Rationale for bone marrow transplantation in the treatment of autoimmune diseases.
Susumu Ikehara,Robert A. Good,Nakamura T,Kenichi Sekita,Shuji Inoue,Maung Maung Oo,Eri Muso,Katsuhiko Ogawa,Yoshihiro Hamashima +8 more
TL;DR: T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune- prone mice.