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CD69+ resident memory T cells are associated with graft-versus-host disease in intestinal transplantation.

ABSTRACT: Graft-versus-host disease (GvHD) is a common, morbid complication after intestinal transplantation (ITx) with poorly understood pathophysiology. Resident memory T cells (T_RM ) are a recently described CD69+ memory T cell subset localizing to peripheral tissue. We observed that T effector memory cells (T_EM ) in the blood increase during GvHD and hypothesized that they derive from donor graft CD69+T_RM migrating into host blood and tissue. To probe this hypothesis, graft and blood lymphocytes from 10 ITx patients with overt GvHD and 34 without were longitudinally analyzed using flow cytometry. As hypothesized, CD4+ and CD8+CD69+T_RM were significantly increased in blood and grafts of GvHD patients, alongside higher cytokine and activation marker expression. The majority of CD69+T_RM were donor derived as determined by multiplex immunostaining. Notably, CD8/PD-1 was significantly elevated in blood prior to transplantation in patients who later had GvHD, and percentages of HLA-DR, CD57, PD-1, and naïve T cells differed significantly between GvHD patients who died vs. those who survived. Overall, we demonstrate that (1) there were significant increases in T_EM at the time of GvHD, possibly of donor derivation; (2) donor T_RM in the graft are a possible source; and (3) potential biomarkers for the development and prognosis of GvHD exist.

SUBMITTER: Weiner J

PROVIDER: S-EPMC10364625 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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CD69+ resident memory T cells are associated with graft-versus-host disease in intestinal transplantation.

Weiner Joshua J Svetlicky Nina N Kang Jiman J Sadat Mohammed M Khan Khalid K Duttargi Anju A Stovroff Merrill M Moturi Sangeetha S Kara Balla Abdalla A Hyang Kwon Dong D Kallakury Bhaskar B Hawksworth Jason J Subramanian Sukanya S Yazigi Nada N Kaufman Stuart S Pasieka Helena B HB Matsumoto Cal S CS Robson Simon C SC Pavletic Steven S Zasloff Michael M Fishbein Thomas M TM Kroemer Alexander A

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20210217 5

Graft-versus-host disease (GvHD) is a common, morbid complication after intestinal transplantation (ITx) with poorly understood pathophysiology. Resident memory T cells (TRM ) are a recently described CD69+ memory T cell subset localizing to peripheral tissue. We observed that T effector memory cells (TEM ) in the blood increase during GvHD and hypothesized that they derive from donor graft CD69+TRM migrating into host blood and tissue. To probe this hypothesis, ...[more]

PMID: 33226726

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Project description:Acute gut graft-versus-host disease (aGVHD) is a leading threat to the survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Abnormal gut microbiota is correlated with poor prognosis in allo-HSCT recipients. A disrupted intestinal microenvironment exacerbates dysbiosis in GVHD patients. We hypothesized that maintaining the integrity of the intestinal barrier may protect gut microbiota and attenuate aGVHD. This hypothesis was tested in a murine aGVHD model and an in vitro intestinal epithelial culture. Millipore cytokine array was utilized to determine the expression of proinflammatory cytokines in the serum. The 16S rRNA sequencing was used to determine the abundance and diversity of gut microbiota. Combining Xuebijing injection (XBJ) with a reduced dose of cyclosporine A (CsA) is superior to CsA alone in improving the survival of aGVHD mice and delayed aGVHD progression. This regimen also reduced interleukin 6 (IL-6) and IL-12 levels in the peripheral blood. 16S rRNA analysis revealed the combination treatment protected gut microbiota in aGVHD mice by reversing the dysbiosis at the phylum, genus, and species level. It inhibited enterococcal expansion, a hallmark of GVHD progression. It inhibited enterococcal expansion, a hallmark of GVHD progression. Furthermore, Escherichia coli expansion was inhibited by this regimen. Pathology analysis revealed that the combination treatment improved the integrity of the intestinal tissue of aGVHD mice. It also reduced the intestinal permeability in aGVHD mice. Besides, XBJ ameliorated doxorubicin-induced intestinal epithelial death in CCK-8 assay. Overall, combining XBJ with CsA protected the intestinal microenvironment to prevent aGVHD. Our findings suggested that protecting the intestinal microenvironment could be a novel strategy to manage aGVHD. Combining XBJ with CsA may reduce the side effects of current aGVHD prevention regimens and improve the quality of life of allo-HSCT recipients.

Dataset Information

CD69+ resident memory T cells are associated with graft-versus-host disease in intestinal transplantation.

Publications

CD69+ resident memory T cells are associated with graft-versus-host disease in intestinal transplantation.

Similar Datasets

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