A locus on chromosome 2 influences the development of acute graft-versus-host disease in a murine model

Harper, J.S.; Slayback, DL; Dobkins, JA; Rw, Allen

doi:10.1038/sj.bmt.1701770

Cited by 4 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[21][22][23] However, our studies indicated that additional loci are involved in predisposing recipients to the development of chronic GVHD. In this report, we describe the results of a linkage analysis aimed at mapping loci at which donor polymorphism influences the development of chronic GVHD.…”

mentioning

confidence: 73%

Genetic factors influencing the development of chronic graft-versus-host disease in a murine model

Slayback

Dobkins

Harper

et al. 2000

Bone Marrow Transplant

Self Cite

View full text Add to dashboard Cite

Summary:Graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation that can occur in either acute or chronic forms. Much of the long-term pathology seen in chronic GVHD is a result of autoantibody production. In the DBA/2 → B6D2F1 murine model of chronic GVHD, anti-ssDNA autoantibodies can be detected by 14 days post cell transfer. These autoantibodies are not observed in B6D2F1 recipients of cells from C57BL/6 or B10.D2 donors, which develop acute rather than chronic GVHD. Therefore, in this model, donor genetic factors predispose to the development of chronic GVHD in recipients. We performed a genetic analysis aimed at mapping donor loci that influence the magnitude of early autoantibody production in B6D2F1 recipients of cells from DBA/2 donor mice. Linkage analysis suggested an influence of two loci: a locus on chromosome 11 linked to D11Mit278 and a locus on chromosome 4 linked to D4Mit226. The locus on chromosome 11 also appeared to influence the development of renal pathology associated with chronic GVHD. Bone Marrow Transplantation (2000) 26, 931-938.

show abstract

mentioning

confidence: 73%

Genetic factors influencing the development of chronic graft-versus-host disease in a murine model

Slayback

Dobkins

Harper

et al. 2000

Bone Marrow Transplant

Self Cite

View full text Add to dashboard Cite

show abstract

“…In that model, we were able to show that the severity of GVHD in a completely MHCmismatched setting depended on the genotype of donor mice at two specific non-MHC loci-one on chromosome 1 and one on chromosome 2. 33,34 Mice with a specific genotype at these loci had a significantly lowered risk of inducing severe acute GVHD, even though they were MHC-mismatched with recipients. 34 This indicates that it is possible to choose donors whose non-MHC genetics will reduce the risk of their cells inducing life-threatening GVHD in recipients, even when there is not a perfect MHC match.…”

Section: Too Many Restrictions On Choosing a Donor?mentioning

confidence: 99%

“…33,34 Mice with a specific genotype at these loci had a significantly lowered risk of inducing severe acute GVHD, even though they were MHC-mismatched with recipients. 34 This indicates that it is possible to choose donors whose non-MHC genetics will reduce the risk of their cells inducing life-threatening GVHD in recipients, even when there is not a perfect MHC match. The implication of this is that, by considering donor immune polymorphism, it may be possible to actually expand the donor pool to include donors without perfect MHC matches but with favorable alleles at functional loci.…”

Section: Too Many Restrictions On Choosing a Donor?mentioning

confidence: 99%

“…Indeed, our studies have indicated that loci on chromosomes 1 and 2, in the vicinity of the Mtv7 and IL-1 loci respectively, influence GVHD development in the B6D2F1 model. [33][34][35] The differential outcome of GVHD in the B6D2F1 model is thought to be due to differential activation of Figure 1 The B6D2F1 parent→F1 murine GVHD model. In this model, transfer of parental strain C57BL/6 lymphoid cells into (C57BL/6 × DBA/2)F1 (ie, B6D2F1) recipients results in acute GVHD whereas transfer of parental strain DBA/2 lymphoid cells into B6D2F1 recipients results in chronic GVHD.…”

Section: Quantity Vs Quality Of T Cell Activationmentioning

confidence: 99%

See 1 more Smart Citation

The new genetics of bone marrow transplantation

2000

Genes Immun

Self Cite

View full text Add to dashboard Cite

There is now little doubt that functional immune polymorphism exists and can exert a significant effect on the severity of immunologic disease. Studies in this area are driven by the belief that an understanding of the influence of immune polymorphism on immunologic disease will improve our ability to predict disease occurrence and severity. The usefulness of this information is necessarily limited, however, by the fact that an individual has a fixed genome. If an individual has an allele which predisposes to increased disease severity, there is little we can do, other than treat the disease in that individual in a more aggressive manner or attempt to find preventative therapies. There is, however, one unique immunologic disorder that is an exception to this rule. Graft-versus-host disease (GVHD), the major complication of bone marrow transplantation, is an immunologic reaction mediated, in large part, by donor T cells. It is unique in that it is the only immunologic disorder in which we can choose the genetics of the immune system causing the disorder. In this disease, more than any other, an understanding of the role of immune polymorphism is essential since we could hypothetically use this information to choose a donor whose T cells will not mediate GVHD of life-threatening severity. In this review, I argue that there is highly suggestive evidence that allelic polymorphism in non-MHC genes encoding mediators of the immune response exerts a very significant effect on the severity of GVHD and that typing for such allelic polymorphisms will in future be as important as MHC-typing in choosing an appropriate donor for bone marrow transplantation. Genes and Immunity (2000) 1, 316-320.

show abstract

“…Some non-MHC loci that modify alloresponse were shown to be minor antigens coded in the mouse by Mtv [13]. Several groups have reported that recognition of a host vSAG (viral superantigens) (Mls1a and Mls2a) by donor T cells may determine the manifestations of GVHD in several parental/F1 strain combinations [14,15], others indicate roles of non-MHC non-Mls genes in MLR [16,17] and in GVHD [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Mouse model for analysis of non-MHC genes that influence allogeneic response: recombinant congenic strains of OcB/Dem series that carry identical H2 locus

et al. 2006

View full text Add to dashboard Cite

Alloreactivity is the strongest known primary immune response. Its clinical manifestations are graft rejection, graft-versus-host disease and graft-versus-leukemia effect. The strongest stimulation by allogeneic cells is due to incompatibility at the major histocompatibility complex (MHC) genes. However, the non-MHC genes also participate in allogeneic response. Here we present a mouse model for study of the role of non-MHC genes in regulation of alloreactivity and show that they besides encoding antigens also regulate the responsiveness. Recombinant congenic strains (RCS) of O20/A (O20)-c-B10.O20/Dem (OcB/Dem) series have been derived from the parental strains O20 and B10.O20, which carry identical MHC haplotypes (H2 pz ) and therefore their differences in alloantigen response depend only on non-MHC genes. We have tested a MLR response by spleen cells of the strains O20, B10.O20, and 16 OcB/Dem strains through stimulation by cells from strains C57BL/10 (H2 b ), BALB/c (H2 d ), CBA (H2 k ), and DBA/1 (H2 q ) alloantigens. Proliferative response of O20, B10.O20 and OcB/Dem strains to these four alloantigens exhibited a similar but not completely identical pattern of reactivity. The responses to different alloantigens were highly correlated: C57BL/10 -BALB/c r = 0.87, C57BL/10 -CBA r = 0.84, C57BL/10 -DBA/1 r = 0.83. Cluster analysis of the responses by O20, B10.O20, and OcB mice identified groups of strains with distinct patterns of response. This data shows that two main types of genes influence MLR: 1. structural genes for major and minor alloantigens and 2. genes regulating T-cell receptor signal transduction or mediating costimulatory signals by antigen-presenting cells.

show abstract

A locus on chromosome 2 influences the development of acute graft-versus-host disease in a murine model

Cited by 4 publications

References 28 publications

Genetic factors influencing the development of chronic graft-versus-host disease in a murine model

Genetic factors influencing the development of chronic graft-versus-host disease in a murine model

The new genetics of bone marrow transplantation

Mouse model for analysis of non-MHC genes that influence allogeneic response: recombinant congenic strains of OcB/Dem series that carry identical H2 locus

Contact Info

Product

Resources

About