BACKGROUND: We previously reported the novel activity of alloprimed CD8 T cells that suppress posttransplant alloantibody production. The purpose of the study is to investigate the expression and role of CXCR5 on antibody-suppressor CD8 T-cell function. METHODS: C57BL/6 mice were transplanted with FVB/N hepatocytes. Alloprimed CD8 T cells were retrieved on day 7 from hepatocyte transplant recipients. Unsorted or flow-sorted (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subsets were analyzed for in vitro cytotoxicity and capacity to inhibit in vivo alloantibody production following adoptive transfer into C57BL/6 or high alloantibody-producing CD8 knock out (KO) hepatocyte transplant recipients. Alloantibody titer was assessed in CD8 KO mice reconstituted with naive CD8 T cells retrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. Antibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific t-cell receptor transgenic CD8+ T cells (OT-I) CXCR5 or CXCR3 CD8 T-cell subsets was also investigated. RESULTS: Alloprimed CXCR5CXCR3CD8 T cells mediated in vitro cytotoxicity of alloprimed "self" B cells, while CXCR3CXCR5CD8 T cells did not. Only flow-sorted alloprimed CXCR5CXCR3CD8 T cells (not flow-sorted alloprimed CXCR3CXCR5CD8 T cells) suppressed alloantibody production and enhanced graft survival when transferred into transplant recipients. Unlike CD8 T cells from wild-type or CXCR3 KO mice, CD8 T cells from CXCR5 KO mice do not develop alloantibody-suppressor function. Similarly, only flow-sorted CXCR5CXCR3 (and not CXCR3CXCR5) OVA-primed OT-I CD8 T cells mediated in vivo suppression of anti-OVA antibody production. CONCLUSIONS: These data support the conclusion that expression of CXCR5 by antigen-primed CD8 T cells is critical for the function of antibody-suppressor CD8 T cells.
BACKGROUND: We previously reported the novel activity of alloprimed CD8 T cells that suppress posttransplant alloantibody production. The purpose of the study is to investigate the expression and role of CXCR5 on antibody-suppressor CD8 T-cell function. METHODS: C57BL/6 mice were transplanted with FVB/N hepatocytes. Alloprimed CD8 T cells were retrieved on day 7 from hepatocyte transplant recipients. Unsorted or flow-sorted (CXCR5CXCR3 and CXCR3CXCR5) alloprimed CD8 T-cell subsets were analyzed for in vitro cytotoxicity and capacity to inhibit in vivo alloantibody production following adoptive transfer into C57BL/6 or high alloantibody-producing CD8 knock out (KO) hepatocyte transplant recipients. Alloantibody titer was assessed in CD8 KO mice reconstituted with naive CD8 T cells retrieved from C57BL/6, CXCR5 KO, or CXCR3 KO mice. Antibody suppression by ovalbumin (OVA)-primed monoclonal OVA-specific t-cell receptor transgenic CD8+ T cells (OT-I) CXCR5 or CXCR3CD8 T-cell subsets was also investigated. RESULTS: Alloprimed CXCR5CXCR3CD8 T cells mediated in vitro cytotoxicity of alloprimed "self" B cells, while CXCR3CXCR5CD8 T cells did not. Only flow-sorted alloprimed CXCR5CXCR3CD8 T cells (not flow-sorted alloprimed CXCR3CXCR5CD8 T cells) suppressed alloantibody production and enhanced graft survival when transferred into transplant recipients. Unlike CD8 T cells from wild-type or CXCR3 KO mice, CD8 T cells from CXCR5 KO mice do not develop alloantibody-suppressor function. Similarly, only flow-sorted CXCR5CXCR3 (and not CXCR3CXCR5) OVA-primed OT-I CD8 T cells mediated in vivo suppression of anti-OVA antibody production. CONCLUSIONS: These data support the conclusion that expression of CXCR5 by antigen-primed CD8 T cells is critical for the function of antibody-suppressor CD8 T cells.
Authors: S M Ensminger; B M Spriewald; H V Sorensen; O Witzke; E G Flashman; A Bushell; P J Morris; M L Rose; A Rahemtulla; K J Wood Journal: J Immunol Date: 2001-07-01 Impact factor: 5.422
Authors: S M Ensminger; B M Spriewald; O Witzke; K Morrison; A van Maurik; P J Morris; M L Rose; K J Wood Journal: Transplantation Date: 2000-09-27 Impact factor: 4.939
Authors: W W Hancock; B Lu; W Gao; V Csizmadia; K Faia; J A King; S T Smiley; M Ling; N P Gerard; C Gerard Journal: J Exp Med Date: 2000-11-20 Impact factor: 14.307
Authors: Jason M Zimmerer; Jing L Han; Chelsea M Peterson; Qiang Zeng; Bryce A Ringwald; Clarissa Cassol; Sachi Chaudhari; Madison Hart; Jessica Hemminger; Anjali Satoskar; Mahmoud Abdel-Rasoul; Jiao-Jing Wang; Robert T Warren; Zheng J Zhang; Christopher K Breuer; Ginny L Bumgardner Journal: Am J Transplant Date: 2022-02-15 Impact factor: 9.369
Authors: Jason M Zimmerer; Matthew W Basinger; Bryce A Ringwald; Mahmoud Abdel-Rasoul; Ronald P Pelletier; Amer Rajab; Ashraf El-Hinnawi; Hemant Parekh; Kenneth Washburn; Ginny L Bumgardner Journal: Transplantation Date: 2020-11 Impact factor: 5.385