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Updated: Aug 8, 2026

Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model
Published on: August 29, 2012
Donor CD4+ T and B cells in transplants induce chronic graft-versus-host disease with autoimmune manifestations
Chunyan Zhang1, Ivan Todorov, Zhifang Zhang
1The Beckman Research Institute, Gonda Building, R2017, City of Hope National Medical Center, 1500 East Duarte Rd, Duarte, CA 91010, USA.
Insights
Chronic graft-vs-host disease (GVHD) involves autoimmune manifestations and can occur without a host thymus. Donor regulatory T cells (Treg) can prevent this process in recipients of allogeneic hemato-poietic cell transplantation (HCT).
Area of Science:
- Immunology
- Transplantation Biology
- Autoimmunity
Background:
- Chronic graft-vs-host disease (GVHD) is a significant complication following allogeneic hemato-poietic cell transplantation (HCT), leading to substantial morbidity and mortality.
- The underlying mechanisms of chronic GVHD, particularly the generation of autoreactive T and B cells, remain poorly understood.
- Chronic GVHD can present with autoimmune features resembling scleroderma and systemic lupus erythematosus (SLE).
Purpose of the Study:
- To investigate the pathogenesis of chronic GVHD, focusing on the role of autoreactive T and B cells.
- To determine if the host thymus is required for the induction of chronic GVHD.
- To evaluate the potential of donor T regulatory cells (Treg) in preventing chronic GVHD.
Main Methods:
- Development of a novel chronic GVHD mouse model using DBA/2 spleen cells transplanted into BALB/c recipients (major histocompatibility complex-matched, minor antigen-mismatched).
- Utilized euthymic, athymic (nu/nu), and adult-thymectomized BALB/c recipients to assess the role of the host thymus.
- Investigated the requirement for specific donor cell populations (CD25-CD4+ T cells, B cells, CD25+CD4+ Treg cells) in disease induction and prevention.
Main Results:
- Both euthymic and athymic BALB/c recipients developed chronic GVHD, characterized by autoantibodies, skin damage, and glomerulonephritis, indicating the host thymus is not required.
- Disease induction necessitated the presence of donor CD25-CD4+ T cells and B cells.
- Transplantation of donor CD25+CD4+ Treg cells effectively prevented chronic GVHD development.
Conclusions:
- Host thymus is dispensable for the induction of chronic GVHD.
- Quiescent autoreactive T and B cells from donors can be activated in allogeneic recipients, leading to autoimmune manifestations of chronic GVHD.
- Donor Treg cells play a crucial suppressive role in mitigating chronic GVHD and its autoimmune sequelae.
Abstract:
Chronic graft-vs-host disease (GVHD) is a major cause of morbidity and mortality of long-term survivors of allogeneic hemato-poietic cell transplantation (HCT). Chronic GVHD can have features of an autoimmune collagen vascular disease with clinical manifestations similar to autoimmune scleroderma and systemic lupus erythematosus (SLE). However, the pathogenesis of chronic GVHD is poorly understood. It is unclear how autoreactive T and B cells are generated in chronic GVHD recipients. We have recently developed a new chronic GVHD model by transplantation of donor DBA/2 (H-2d) spleen cells into major histocompatibility complex (MHC)-matched but minor antigen-mismatched sublethally irradiated BALB/c (H-2d) recipients as well as athymic BALB/c(nu/nu) and adult-thymectomized BALB/c recipients. Both euthymic and athymic BALB/c recipients developed high levels of serum IgG autoantibodies, sclerodermatous skin damage, and glomerulonephritis. Disease induction required both donor CD25-CD4+ T and B cells in transplants. In contrast, donor CD25+CD4+ T regulatory (Treg) cells prevented the disease induction. These results indicate that host thymus is not required for induction of chronic GVHD and that quiescent autoreactive T and B cells in transplants from nonautoimmune donors may be activated and expanded to cause chronic GVHD with autoimmune manifestations in allogeneic recipients, and donor Treg cells can suppress this process.
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