CD98 heavy chain (CD98hc), encoded by Slc3a2, is a widely expressed vertebrate membrane protein whose functions are known as facilitating amino acid transporter and mediating integrin signaling. Little is known about its function on T lymphocyte mediated immune response to alloantigen. Here we report that we successfully deleted CD98hc in T-cells by crossing mice bearing a loxP-flanked Slc3a2 allele with those expressing Cre recombinase in T cells (CD4-Cre+). Adoptive transfer of control C57BL/6 (B6, H-2Kb) mice spleen lymphocytes (1×108 cells) into (B6xDBA, H-2Kb,d) BDF1 undergoing graft-versus-host disease (GvHD) lethality (MST: 19.8 days±5, n=7), accompany with body weight loss significantly. In contrast, adoptive transfer of CD98hc deficient (B6, H-2Kb) mice spleen lymphocytes showed potent inhibition of lethality (MST: >100days, n=7), without body weight loss. Furthermore, FACS analysis data revealed that donor B6 lymphocytes were increased significantly in recipient compared with CD98hc deficient mice. Hence our data indicated that T cell-specific deficient of CD98hc impaired proliferate in response to alloantigens result in inducing immune tolerance after T-cell transfer. This finding has important implications for clarifying the mechanism of GvHD and to block of CD98hc by monoclonal antibody may be effective for treatment of GvHD clinically in the future.
To cite this abstract in AMA style:Li X, Kitajima Y, Nishio Y, Saito T, Tsumura H, Nagahara Y, Cai S. Deletion of CD98hc in Lymphocytes Results in Increasing Treg Cell To Prevent Acute Murine GvHD [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/deletion-of-cd98hc-in-lymphocytes-results-in-increasing-treg-cell-to-prevent-acute-murine-gvhd/. Accessed November 27, 2020.
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