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.

Blood
|December 15, 2005
PubMed

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.

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