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Major histocompatibility complex class 1-related gene protein (MR1) is a monomorphic antigen-presenting molecule. Mucosal associated invariant T (MAIT) cells are an unconventional T cells subset limited to the antigen-presenting molecule MR1. MR1 rs2236410 site of single nucleotide polymorphism (SNP) is reported that locates in the MR1 antigen binding region and is identified as HLA Class II restricted minor histocompatibility antigen, which is associated with transplantation immunity. Here, we found that the donor rs2236410A/G genotype was associated with a lower incidence of severe or gut acute graft-versus-host disease (GVHD) in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) clinical cohort. Through in vitro E. colistimulation experiments, it was found that MR1 rs2236410 mediated the activation of MR1-dependent pathway of MAIT cells by influencing the presentation of microbial derived ligand, thus affecting the anti-GVHD effect of MAIT cells. These findings suggest that MR1 rs2236410 could serve as a potential immune target for antiGVHD without affecting the GVL effect in the context of transplantation, which could provide certain guidance for the prediction and clinical treatment of GVHD.

Additional file 2: Supplementary Figures

The pinewood nematode Bursaphelenchus xylophilus (B. xylophilus) is responsible for a devastating disease of pine forests. Its pathogenicity is closely related to the numbers of individual B. xylophilus. The ratio of female to male (sex ratio) is key to understanding population change in this species. The sex ratio of B. xylophilus varies widely, but it is unclear how it is affected by environmental changes. The sex ratios of nematodes, isolated from different samples in the wild, varied between 0.93 and 2.20. Under laboratory conditions, maternal age and the population did not affect the sex ratio of progeny. A change from good to poor nutritional status was associated with a reduction of the sex ratio of progeny from 1.85 to 1.41, which was speculated to result from a change in the primary sex ratio. Thus, B. xylophilus effectively maintains the sex ratio with maternal age and population changes but adjusts the sex ratio of progeny on the basis of the changes in nutrition.

Background & Purpose: Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosal-associated invariant T cells (MAITs) are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT in the occurrence of gut aGVHD in the human body. Methods & Cases: In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells (MAITs) and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyse the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAITs. The number and distribution of MAITs in intestinal tissues were analysed by immunofluorescence technology. We prospectively studied the enrolled 150 consecutive patients who underwent allo-HSCT in our institute. Results: The number and frequency of MAITs in infused grafts in gut aGVHD patients were lower than those in non-gut aGVHD patients (Figure). Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early post-transplantation period (+14 days). At the onset of gut aGVHD, the number of MAITs decreased in peripheral blood, and the activation marker CD69, chemokines CXCR3 and CXCR4 and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAITs secreted more granzyme B, TNF-α and IFN-γ under the stimulation of IL-12/IL-18 (non-TCR signal) and secreted most of the IL-17 under the stimulation of CD3/CD28 (TCR signal). MAITs inhibited the proliferation of CD4+ T cells in vitro. Conclusions: In conclusion, the lower number of MAITs in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAITs in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAITs and promoted the secretion of intestinal protective factors to affect the occurrence of gut aGVHD in humans. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background & Purpose: Gut graft-versus-host disease (GVHD) is a serious complication after hematopoietic stem cell transplantation (HSCT) and is associated with high mortality. Mucosal-associated invariant T cells (MAIT) are a group of innate-like T cells enriched in the intestine, which may alter the composition of the intestinal microflora or exert a certain immunomodulatory effect to protect the intestinal mucosa from further damage for the inflammatory response. However, little is known about the regulatory role of MAIT cells in development and progression of gut GVHD. Infused MAIT in grafts will facilitate the reconstruction of MAIT after transplantation. Thus, we aimed to investigate the correlation between the number of MAIT cells in the graft and the occurrence of gut GVHD. Methods & Cases: Our transplantation setting used the graft composed of bone marrow stem cells (BMSC) and peripheral blood stem cell (PBSC). We prospectively studied 60 patients undergoing allo-HSCT and 9 healthy donors in our institute. In our study, the number of MAIT cells in the graft was evaluated by multiparameter flow cytometry (FCM). MAIT cells were defined as a group of cells expressing CD3+CD161hiVa7.2+. To better compare the specific changes in the number of MAIT cells in the graft in groups of healthy donors, no GVHD patients, skin GVHD patients, and gut GVHD patients, we chose a group of non-MAIT cells that express CD3+CD161-Va7.2+ as a reference(Fig.1A). We compared the number and frequency of MAIT and non-MAIT cells in the 4 groups. Results: In the 60 transplanted patients, 9 patients developed into gut GVHD and 6 patients developed into skin GVHD. In patients with gut GVHD, the frequency of MAIT cells in the graft of PBSC was lower compared to that of no GVHD (No GVHD vs. gut GVHD, P=0.045. Fig.1B), but no difference was detected in the graft of BMSC among these groups (No GVHD vs. gut GVHD, P=0.191; Healthy vs. gut GVHD, P=0.298; Skin GVHD vs. gut GVHD, P=0.071. Fig.1C). The total number of infused MAITs in the graft of gut GVHD patients was significantly lower than that of no GVHD and skin GVHD patients (no GVHD vs. gut-GVHD, P=0.001. Fig.1D). In addition, the frequency and number of MAIT cells in the graft were not different between no GVHD and skin GVHD patients (P>0.05, Fig.1B, C and D). Finally, in the graft of patients with no GVHD, skin GVHD and gut GVHD, the difference in the frequency and number of non-MAIT cells was not significant (all P>0.05, Fig.1E and Fig.1F). Conclusions: In conclusion, gut GVHD was more likely to occur in patients who were infused with a smaller number of MAIT cells in grafts. In addition, the number of MAIT cells in the graft had no significant correlation with the occurrence of skin GVHD. These results suggested the potential functional effects of MAIT cells on gut GVHD. However, the specific biological role of MAIT cells in maintaining the homeostasis of intestinal tract and how MAIT cells would influence the onset of gut GVHD are still unclear. It may function through direct immunosuppression or regulation of intestinal microflora, which needs to be confirmed by further mechanical studies. Figure 1 Disclosures No relevant conflicts of interest to declare.