BACKGROUND: Inducible costimulator (ICOS), a member of the CD28 family of costimulatory molecules, is induced on CD4 and CD8 T cells after their activation. ICOS functions as an essential immune regulator and ICOS blockade is a potential approach to immune modulation in allogeneic transplantation. Here, we describe the expression profile of ICOS in dogs and determine whether ICOS expression is up-regulated during chronic graft-versus-host disease (GVHD) and host-versus-graft reactions in the canine hematopoietic cell transplantation model. METHODS: Monoclonal antibodies (mAbs) against cell surface-expressed ICOS were produced and tested in vitro for suppression of canine mixed leukocyte reactions (MLR). Expression of ICOS on CD3 cells was evaluated by flow cytometry using peripheral blood, lymph nodes, and splenocytes obtained from dogs undergoing graft-versus-host and host-versus-graft reactions. RESULTS: Canine ICOS was expressed in an inducible pattern on T cells activated by concanavalin A, anti-CD3 mAb in combination with anti-CD28 mAb, and alloantigen stimulation. Immunosuppressive effects of ICOS blockade were observed in MLR using peripheral blood mononuclear cells from dog leukocyte antigen-nonidentical dogs. Immunosuppressive effects of ICOS blockade were observed in MLR when anti-ICOS was combined with suboptimal concentrations of cytotoxic T-lymphocyte antigen 4-Ig or cyclosporine. ICOS expression was significantly up-regulated on T cells in dogs undergoing graft rejection or chronic GVHD after allogeneic hematopoietic cell transplantation. CONCLUSIONS: These studies suggest that ICOS plays a role in graft rejection and GVHD in an outbred animal model, and ICOS blockade may be an approach to prevention and treatment of chronic GVHD.
BACKGROUND:Inducible costimulator (ICOS), a member of the CD28 family of costimulatory molecules, is induced on CD4 and CD8 T cells after their activation. ICOS functions as an essential immune regulator and ICOS blockade is a potential approach to immune modulation in allogeneic transplantation. Here, we describe the expression profile of ICOS in dogs and determine whether ICOS expression is up-regulated during chronic graft-versus-host disease (GVHD) and host-versus-graft reactions in the canine hematopoietic cell transplantation model. METHODS: Monoclonal antibodies (mAbs) against cell surface-expressed ICOS were produced and tested in vitro for suppression of canine mixed leukocyte reactions (MLR). Expression of ICOS on CD3 cells was evaluated by flow cytometry using peripheral blood, lymph nodes, and splenocytes obtained from dogs undergoing graft-versus-host and host-versus-graft reactions. RESULTS:CanineICOS was expressed in an inducible pattern on T cells activated by concanavalin A, anti-CD3 mAb in combination with anti-CD28 mAb, and alloantigen stimulation. Immunosuppressive effects of ICOS blockade were observed in MLR using peripheral blood mononuclear cells from dog leukocyte antigen-nonidentical dogs. Immunosuppressive effects of ICOS blockade were observed in MLR when anti-ICOS was combined with suboptimal concentrations of cytotoxic T-lymphocyte antigen 4-Ig or cyclosporine. ICOS expression was significantly up-regulated on T cells in dogs undergoing graft rejection or chronic GVHD after allogeneic hematopoietic cell transplantation. CONCLUSIONS: These studies suggest that ICOS plays a role in graft rejection and GVHD in an outbred animal model, and ICOS blockade may be an approach to prevention and treatment of chronic GVHD.
Authors: Jennifer L Berrie; Maciej Kmieciak; Roy T Sabo; Catherine H Roberts; Michael O Idowu; Katherine Mallory; Harold M Chung; John M McCarty; Christian A Borrelli; Michelle M Detwiler; A Latif Kazim; Amir A Toor; Masoud H Manjili Journal: Transplantation Date: 2012-05-15 Impact factor: 4.939
Authors: G E Georges; R Storb; B Bruno; S J Brodie; J D Thompson; A G Taranova; J M Zaucha; M T Little; E Zellmer; P F Moore; T Gooley; G Sale; H P Kiem; B M Sandmaier; R M Lyons; R A Nash Journal: Blood Date: 2001-12-01 Impact factor: 22.113
Authors: A J McAdam; T T Chang; A E Lumelsky; E A Greenfield; V A Boussiotis; J S Duke-Cohan; T Chernova; N Malenkovich; C Jabs; V K Kuchroo; V Ling; M Collins; A H Sharpe; G J Freeman Journal: J Immunol Date: 2000-11-01 Impact factor: 5.422
Authors: H J Deeg; R Storb; P L Weiden; R F Raff; G E Sale; K Atkinson; T C Graham; E D Thomas Journal: Transplantation Date: 1982-07 Impact factor: 4.939
Authors: Scott S Graves; Maura H Parker; Diane Stone; George E Sale; Smitha P S Pillai; Melissa M Johnson; Rainer Storb Journal: Biol Blood Marrow Transplant Date: 2017-09-25 Impact factor: 5.742
Authors: Lin Yan; Kitty de Leur; Rudi W Hendriks; Luc J W van der Laan; Yunying Shi; Lanlan Wang; Carla C Baan Journal: Front Immunol Date: 2017-11-07 Impact factor: 7.561