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

Abstract

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.

Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease

“…Several parent 3 F1 transplantation models, while described as cGVHD models, result in a disease more similar to systemic lupus erythematosus than cGVHD. [33][34][35][36] 49 Although this model is best viewed as a de novo model of cGVHD, its value lies in the strong resemblance to the clinicopathologic features found in both primary and secondary cGVHD in humans.…”

“…Several parent 3 F1 transplantation models, while described as cGVHD models, result in a disease more similar to systemic lupus erythematosus than cGVHD. [33][34][35][36] However, the B10.D2 (H-2 d ) 3 BALB/c (H-2 d ) MHC-compatible, multiple minor histocompatibility antigen (miHA)-incompatible model of cGVHD [37][38][39][40][41] does share critical characteristics with human cGVHD. Its dominant features include skin fibrosis (due to increased collagen deposition) as well as lichenoid subepithelial infiltrates, follicular drop-out, loss of subdermal fat, and dermal mononuclear infiltrates.…”

“…Several parent 3 F1 transplantation models, while described as cGVHD models, result in a disease more similar to systemic lupus erythematosus than cGVHD. [33][34][35][36] 49 Although this model is best viewed as a de novo model of cGVHD, its value lies in the strong resemblance to the clinicopathologic features found in both primary and secondary cGVHD in humans.In general, most GVHD research-whether using acute or chronic models-has focused on the properties of donor T cells, and less attention has been given to host factors that might influence the incidence and character of GVHD. However, several studies have shown that recipient cells can indeed affect GVHD.…”

Scavenger receptor expressions in the kidneys of mice with lipoprotein glomerulopathy

“…Injection of lymphocytes of Bm12 mice into C57BL/6 mice leads to cGVHD and a SLE-like disease [19,20]. These human SLE-like animals were mainly characterized by immune complex-mediated glomerulonephritis.…”

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

“…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].…”