title: Host-based Th2 cell therapy for prolongation of cardiac allograft viability.
abstract: Donor T cell transfusion, which is a long-standing approach to prevent allograft rejection, operates indirectly by alteration of host T cell immunity. We therefore hypothesized that adoptive transfer of immune regulatory host Th2 cells would represent a novel intervention to enhance cardiac allograft survival. Using a well-described rat cardiac transplant model, we first developed a method for ex vivo manufacture of rat host-type Th2 cells in rapamycin, with subsequent injection of such Th2.R cells prior to class I and class II disparate cardiac allografting. Second, we determined whether Th2.R cell transfer polarized host immunity towards a Th2 phenotype. And third, we evaluated whether Th2.R cell therapy prolonged allograft viability when used alone or in combination with a short-course of cyclosporine (CSA) therapy. We found that host-type Th2.R cell therapy prior to cardiac allografting: (1) reduced the frequency of activated T cells in secondary lymphoid organs; (2) shifted post-transplant cytokines towards a Th2 phenotype; and (3) prolonged allograft viability when used in combination with short-course CSA therapy. These results provide further support for the rationale to use "direct" host T cell therapy for prolongation of allograft viability as an alternative to "indirect" therapy mediated by donor T cell infusion.
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America. samarnath@mail.nih.gov
authors.forename: Shoba
authors.initials: S
authors.lastname: Amarnath
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Jason E
authors.initials: JE
authors.lastname: Foley
authors.forename: Carliann M
authors.initials: CM
authors.lastname: Costanzo
authors.forename: Joel D
authors.initials: JD
authors.lastname: Sennesh
authors.forename: Michael A
authors.initials: MA
authors.lastname: Solomon
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D010641:Phenotype; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus