Role of T cell immune response cDNA 7 on the pathology of acute graft‑versus‑host disease

Abstract

Activation of T lymphocytes is the initiating factor of the occurrence of acute graft-versus-host disease (aGVHD), and cytotoxic T lymphocyte antigen-4 (CTLA-4) is the inhibitory receptor for activating T cells. T cell immune response cDNA 7 (TIRC7) is considered an upstream regulator of CTLA-4; however, little is understood regarding the effects of TIRC7 on the regulation of CTLA-4 in aGVHD. The purpose of the present study was to evaluate the regulatory effects of TIRC7 on aGVHD, mainly in the pathology. Recipient mice were exposed to a preconditioning dose of 7.5 Gy irradiation on the day of the transplantation and were divided into the following groups: Blank control group, bone marrow transplantation control group, total body irradiation group, mild-moderate aGVHD group and severe aGVHD group. According to the different administration of CTLA-4 and TIRC7 monoclonal antibodies, the mild-moderate and severe aGVHD groups were randomly divided into the hematopoietic stem cell transplantation (HSCT) and HSCT + CTLA-4/TIRC7 groups. Recipient mice were sacrificed at different time points post-HSCT for histopathological analysis by hematoxylin and eosin staining. Compared with the control and other experimental groups, the mice in the combined CTLA-4 and TIRC7 group exhibited ameliorated pathological injury, and lower pathology scores of the liver, lung and intestine. These data revealed that intraperitoneal injection of anti-TIRC7 and/or anti-CTLA-4 monoclonal antibody into mice could effectively alleviate the severity of aGVHD.

The Transmembrane Receptor TIRC7 Identifies a Distinct Subset of Immune Cells with Prognostic Implications in Cholangiocarcinoma

“…In 2006, we demonstrated that TIRC7 colocalizes with CTLA-4 in human T cells and showed that the TIRC7-induced inhibitory effects on T cells are dependent on CTLA-4 expression, as a blockade of CTLA-4 completely abolished TIRC7-mediated effects [ 38 ]. A similar finding was reported on lymphocytes from patients with acute graft-versus-host disease by Zhu et al, who concluded that TIRC7 inhibits T cell activation by upregulation of CTLA-4 [ 39 ]. Given the breakthrough advancements achieved by inhibition of CTLA-4 in several advanced tumor entities and the evidence on its functional relation to TIRC7, TIRC7 should be considered a potential new upstream molecule to be addressed therapeutically in CCA and other solid tumors.…”

Immune Regulatory 1 Cells: A Novel and Potent Subset of Human T Regulatory Cells

“…TIRC7 appears to play a key role in graft versus host disease ( 16 ), allograft rejection ( 17 ) and autoimmune disorders ( 9 ). During solid organ transplant rejection, TIRC7 expression is increased in the allograft and decreased in peripheral blood lymphocytes ( 18 ).…”