EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Irradiated donor leukocytes promote engraftment of allogeneic bone marrow in major histocompatibility complex mismatched recipients without causing graft-versus-host disease



Irradiated donor leukocytes promote engraftment of allogeneic bone marrow in major histocompatibility complex mismatched recipients without causing graft-versus-host disease



Blood 94(9): 3222-3233



Graft rejection in allogeneic bone marrow transplantation (BMT) can occur when donor and recipient are mismatched at one or more major histocompatibility complex (MHC) loci. Donor T cells can prevent graft rejection, but may cause fatal graft-versus-host disease (GVHD). We tested whether irradiation of allogeneic donor lymphocytes would preserve their graft-facilitating activity while inhibiting their potential for GVHD. Infusions of irradiated allogeneic T cells did not cause GVHD in MHC-mismatched SJL --> (SJL x C57BL6) F1, C57BL6 --> B10.RIII, and C57BL6 --> B10.BR mouse donor --> recipient BMT pairs. The 60-day survival among MHC-mismatched transplant recipients increased from 2% (BM alone) to up to 75% among recipients of BM plus irradiated allogeneic splenocytes. Optimal results were obtained using 50 x 10(6) to 75 x 10(6) irradiated donor splenocytes administered in multiple injections from day -1 to day +1. Recipients of an equal number of nonirradiated MHC-mismatched donor splenocytes uniformly died of acute GVHD. The graft facilitating activity of the irradiated allogeneic splenocytes was mediated by donor T cells. Irradiation to 7.5 Gy increased nuclear NFkappaB in T cells and their allospecific cytotoxicity. Irradiated T cells survived up to 3 days in the BM of MHC-mismatched recipients without proliferation. Recipients of irradiated allogeneic splenocytes and allogeneic BM had stable donor-derived hematopoiesis without a significant representation of donor splenocytes in the T-cell compartment. Irradiated allogeneic T cells thus represent a form of cellular immunotherapy with time-limited biologic activity in vivo that can facilitate allogeneic BMT without causing GVHD.

(PDF emailed within 1 workday: $29.90)

Accession: 010885593

Download citation: RISBibTeXText

PMID: 10556211



Related references

Major histocompatibility complex-mismatched allogeneic bone marrow transplantation using perforin and/or Fas ligand double-defective CD4(+) donor T cells: involvement of cytotoxic function by donor lymphocytes prior to graft-versus-host disease pathogenesis. Blood 98(2): 390-397, 2001

Allo-major histocompatibility complex-restricted cytotoxic T lymphocytes engraft in bone marrow transplant recipients without causing graft-versus-host disease. Blood 94(9): 2999-3006, 1999

Improved engraftment with minimal graft-versus-host disease after major histocompatibility complex-mismatched cord blood transplantation with photochemically treated donor lymphocytes. Experimental Biology and Medicine 236(4): 492-504, 2011

Treatment of donor mice with an alpha beta T-cell receptor monoclonal antibody induces prolonged T-cell nonresponsiveness and effectively prevents lethal graft-versus-host disease in murine recipients of major histocompatibility complex (MHC)-matched and MHC-mismatched donor marrow grafts. Blood 87(12): 5355-5369, 1996

Engraftment of T-depleted major histocompatibility complex-mismatched bone marrow in T-deficient versus natural killer-deficient recipients. Scandinavian Journal of Immunology 29(5): 627-629, 1989

Mesenchymal stromal cells fail to alleviate experimental graft-versus-host disease in rats transplanted with major histocompatibility complex-mismatched bone marrow. Scandinavian Journal of Immunology 76(5): 464-470, 2012

Major histocompatibility complex influences the development of acute graft-versus-host disease in MHC-matched adult allogeneic bone marrow transplantation. Transplantation Proceedings 25(1 Pt 2): 1276-1278, 1993

The effect of G-CSF-stimulated donor marrow on engraftment and incidence of graft-versus-host disease in allogeneic bone marrow transplantation. Clinical Transplantation 15(5): 317-323, 2001

Bone Marrow Graft-Versus-Host Disease in Major Histocompatibility Complex-Matched Murine Reduced-Intensity Allogeneic Hemopoietic Cell Transplantation. Transplantation 101(11): 2695-2704, 2017

A correlation between conditioning and engraftment in recipients of major histocompatibility complex mismatched t cell depleted murine bone marrow transplants. Journal of Immunology 135(2): 941-946, 1985

Alloantigen-specific T-cell depletion in a major histocompatibility complex fully mismatched murine model provides effective graft-versus-host disease prophylaxis in the presence of lymphoid engraftment. British Journal of Haematology 118(1): 108-116, July, 2002

Linkage analysis of minor histocompatibility genes causing graft-versus-host disease following allogeneic bone marrow transplantation. American Journal of Human Genetics 71(4 Supplement): 431, October, 2002

Interleukin-12 prevents severe acute graft-versus-host disease (GVHD) and GVHD-associated immune dysfunction in a fully major histocompatibility complex haplotype-mismatched murine bone marrow transplantation model. Transplantation 64(9): 1343-1352, 1997

Attenuation of Hepatic Graft-versus-host Disease in Allogeneic Recipients of MyD88-deficient Donor Bone Marrow. Immune Network 15(3): 125-134, 2015

Genetics of graft-versus-host disease, I. locus on chromosome 1 influences development of acute graft-versus-host disease in a major histocompatibility complex mismatched murine model. Immunology 96(2): 254-261, 1999