Biomaterial Database

Prevention and restoration of second-set liver allograft rejection in presensitized mice: the role of "passenger" leukocytes, donor major histocompatibility complex antigens, and host cytotoxic effector mechanisms. 1999

F Fu, and W Li, and L Lu, and A W Thomson, and J J Fung, and S Qian

Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, Pennsylvania 15213, USA.

BACKGROUND The aim was to determine whether sublethal donor total body irradiation (TBI) might be as effective as lethal TBI in preventing mouse second-set liver allograft rejection, and to evaluate the role of passenger leukocytes, donor major histocompatibility complex (MHC) antigens, and host effector mechanisms in the response to livers from sublethally irradiated donors. METHODS B10 (H2b) donors received various doses of TBI at different times before their livers were transplanted orthotopically into normal or donor skin-presensitized C3H (H2k) recipients. The influence of irradiation on graft non-parenchymal cells (NPC) was determined by monoclonal antibody staining, and flow cytometric analysis. Hematopoietic cells within the grafts were reconstituted by intravenous infusion of syngeneic or third-party bone marrow cells. Allograft survival was determined in recipients that received no treatment, or that were given spleen cells from either normal B10 donors, or MHC class I - or class II-deficient mice syngeneic with the donors. Cytotoxic activity of graft-infiltrating cells and host spleen cells, and complement-dependent cytotoxic alloantibody titers were determined by isotype release assays. RESULTS The protective effect of donor TBI was observed both at lethal (9.5 Gy) and sublethal doses (5 and 3 Gy; graft median survival time: >100 days). Extended delay in liver transplantation, allowing hematopoietic recovery and graft reconstitution eliminated the effect. Liver NPC were reduced about 80% within 24 hr of 3 Gy TBI, with a selective reduction in the incidence of B cells. The NPC-depleted livers underwent accelerated rejection when donor (but not third-party) spleen cells (5 x 10(7) were administered systemically to the recipient immediately after graft revascularization. Spleen cells from MHC class I-deficient (but not MHC class II-deficient) mice failed to fully restore accelerated rejection of TBI liver grafts. Freshly isolated graft NPC, or spleen cells from TBI liver recipients, harvested 4 days after transplantation, exhibited lower, donor-specific cytotoxic activity than cells from mice given normal livers. Recipients of TBI livers also showed much lower serum complement-dependent cytotoxic alloantibody titers. CONCLUSIONS By substantially depleting "passenger leukocytes," sublethal donor TBI undermines anti-donor cell-mediated and humoral immune reactivity and inhibits second-set liver allograft rejection in presensitized recipients. The interval between irradiation and transplantation is important in conferring resistance to rejection. Expression of MHC class I on donor leukocyte infusions is important for overcoming resistance to second-set rejection induced by donor irradiation.

UI	MeSH Term	Description	Entries
D007165	Immunosuppression Therapy	Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.	Antirejection Therapy,Immunosuppression,Immunosuppressive Therapy,Anti-Rejection Therapy,Therapy, Anti-Rejection,Therapy, Antirejection,Anti Rejection Therapy,Anti-Rejection Therapies,Antirejection Therapies,Immunosuppression Therapies,Immunosuppressions,Immunosuppressive Therapies,Therapies, Immunosuppression,Therapies, Immunosuppressive,Therapy, Immunosuppression,Therapy, Immunosuppressive
D007518	Isoantibodies	Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.	Alloantibodies
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008285	Major Histocompatibility Complex	The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.	Histocompatibility Complex,Complex, Histocompatibility,Complex, Major Histocompatibility,Complices, Histocompatibility,Complices, Major Histocompatibility,Histocompatibility Complex, Major,Histocompatibility Complices,Histocompatibility Complices, Major,Major Histocompatibility Complices
D008297	Male		Males
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008809	Mice, Inbred C3H	An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research.	Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D003602	Cytotoxicity, Immunologic	The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.	Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D005434	Flow Cytometry	Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.	Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell