Graft versus self (GvS) against T-cell autoantigens is a mechanism of graft–host interaction

Abstract

Graft-versus-host disease (GVHD) represents the major nonrelapse complication of allogeneic hematopoietic cell transplantation. Although rare, the CNS and the eye can be affected. In this study, manifestation in the retina as part of the CNS and T-cell epitopes recognized by the allogeneic T cells were evaluated. In 2 of 6 patients with posttransplantation retina diseases and 6 of 22 patients without ocular symptoms, antigen-specific T-cell responses against retina-specific epitopes were observed. No genetic differences between donor and recipient could be identified indicating T-cell activation against self-antigens (graft versus self). Transplantation of a preexisting immunity and cross-reactivity with ubiquitous epitopes was excluded in family donors and healthy individuals. In summary, an immunological reaction against retina cells represents a mechanism of graft-versus-host interaction following hematopoietic cell transplantation.

T-Cell Metabolism in Hematopoietic Cell Transplantation

“… (A) Naïve/resting T cells are dependent on oxidative phosphorylation with fatty acid oxidation (FAO) as a major material resource. Upon activation by self-antigens under homeostatic state, naïve/resting T cells reprogram their metabolic phenotype to become partially activated T cells ( 29 ), which possess glycolytic metabolic phenotype. Due to lack of specific TCR stimulation, a large proportion of non-alloreactive T cells gradually die.…”

“…These inconsistent observations likely result from the different controls used in these two studies. While studies from Ferrara’s group compared bioenergetic parameters of allogeneic T cells to naïve/resting T cells ( 9 ), we used those isolated from syngeneic recipients as controls ( 2 ); intended to account for homeostatic proliferation of T cells under an inflammatory environment ( 29 ). In addition, we observed both Glut1 and Glut3 expression could serve as indicators of glycolytic activity ( 9 ), as alloreactive T cells increase Glut3 to an even larger extent than Glut1 in allogeneic recipients ( 2 ).…”

Advances in understanding the pathogenesis of graft‐versus‐host disease

“…Bacterial colonization of the classical GVHD target organs, skin and intestinal tract, as well as liver draining the lymphoid fluid from the intestinal tract has led to the hypothesis that bacterial transmigration is essential for the disease. In other organs affected by GVHD, such as the gonads, lungs, central nervous system and retina cells (Hartrampf et al , ; Kaliyaperumal et al , ; Mirza et al , ; Grønningsæter et al , ) other pathomechanisms, that are not related to microbiota, may be active.…”

Manifestation of Clinical Categories of Ocular Graft-versus-Host Disease

“…Graft-versus-host disease (GVHD), an immune-mediated disease caused by complex interactions between donor and recipient immune systems, is a leading cause of morbidity and mortality following HSCT [ 4 , 6 , 7 ]. The 2014 National Institutes of Health Consensus recognized 2 principal categories of GVHD (acute and chronic) according to clinical features rather than the temporal relationship to the time of transplantation.…”