scholarly journals Haptens can serve as surrogate transplantation antigens in a manner that demonstrates H-2 restriction of graft rejection.

1983 ◽  
Vol 157 (4) ◽  
pp. 1354-1359 ◽  
Author(s):  
J W Streilein ◽  
P R Bergstresser
Keyword(s):  
Graft Rejection ◽  
Model System ◽  
Skin Grafts ◽  
Transplantation Immunity ◽  
Transplantation Antigens

Hapten-immune mice are capable of rejecting syngeneic skin grafts that are derivatized with the relevant hapten, but only if the hapten is applied while the graft is "healing in." This model system was used to demonstrate that the hapten-specific immune effectors responsible for rejection are restricted by H-2 determinants of the recipient. Thus, haptens can be used in vivo as surrogate transplantation antigens for the study of immunopathogenic mechanisms in transplantation immunity.

scholarly journals Histocompatibility antigens controlled by the I region of the murine H-2 complex. I. Mapping of H-2A and H-2C loci.

1976 ◽  
Vol 143 (6) ◽  
pp. 1439-1452 ◽  
Author(s):  
J Klein ◽  
R Geib ◽  
C Chiang ◽  
V Hauptfeld
Keyword(s):  
Skin Grafting ◽  
Skin Grafts ◽  
Spleen Cells ◽  
Histocompatibility Antigens ◽  
Congenic Lines ◽  
Central Regions ◽  
Transplantation Antigens

Skin grafts were reciprocally exchanged in pairs of congenic lines identical in all genes except those located in the central portion of the H-2 complex. Seven such lines were tested: 6R, B10.AQR, A.TL, A.TH, 7R, 9R, and B10.HTT. In all donor-recipient combinations at least some grafts were rejected. In combinations differing at the IA subregion (and other central H-2 regions or subregions), all first-set grafts were rejected within 3 wk after transplantation, and all second-set grafts were rejected within 10 days. In combinations differing at the IC subregion (and other central regions, but not at the IA subregion) between 60 and 100% of first-set grafts were rejected, but some grafts survived for over 100 days. Most of the second-set grafts were rejected within 1 mo after grafting. This behavior of skin grafts indicated the presence of two histocompatibility loci in the I region, a strong one and a weak one. This conclusion was confirmed by genetic mapping which placed the strong locus in the IA subregion and the weak locus in the IC subregion. We designate the former locus H-2A and the latter H-2C. The same strain combinations used for the skin grafting were also used for determination of the capacity of I-region antigens to function as targets in the in vitro cell-mediated lymphocytotoxicity (CML) assay. Spleen cells from mice presensitized in vivo by skin grafting were restimulated in vitro and tested against 51Cr-labeled concanavalin A or lipopolysaccharide blasts. The testing revealed the presence in the I region of two loci coding for CML-target antigens. The two loci comapped with the H-2A and H-2C loci and were most likely identical to them. As in the skin grafting test, in the CML test, the H-2A antigens evoked stronger response than the H-2C antigens. Rejection of skin grafts across the H-2A and H-2C loci was accompanied by the production of Ia antibodies. Direct cytotoxic and absorption tests with Ia antibodies directed against antigens coded for by the IC subregion revealed the presence of IaC antigens on epidermal cells. We suggest that the products of Ia loci might function as transplantation antigens.

In the Absence of Preformed Antibody, Sensitized T Cells Mediate an Increased Barrier to Engraftment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 191-191
Author(s):  
Hong Xu ◽  
Paula M. Chilton ◽  
Yiming Huang ◽  
Carrie L. Schanie ◽  
Michael K. Tanner ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Humoral Immunity ◽  
Graft Rejection ◽  
Bone Marrow Cells ◽  
Skin Grafts ◽  
Relative Contribution ◽  
Marrow Cells

Abstract Allosensitization resulting from transfusion therapy is a major challenge for the use of bone marrow transplantation to treat sickle cell disease. Prior exposure to foreign major histocompatibility complex (MHC) antigens through transfusion or transplantation is associated with an increased rate of solid organ graft rejection. Using a mouse model for sensitization, we recently found that humoral immunity plays a dominant role in sensitization to MHC alloantigens and concomitant graft rejection. The relative contribution of cellular versus humoral adaptive immune responses has not been fully characterized. In this study, we explored the role of host T cells in rejection of allografts by sensitized recipients using μ MT mice which are defective in producing mature B cells and antibody. Therefore, the barrier from preformed antibodies in sensitized normal mice would not exist in μ MT mice. μ MT (H-2b) mice were sensitized with BALB/c (H-2d) skin grafts. Although no anti-MHC alloantibody was detected in the μ MT mice after rejection, the skin grafts were rejected with a kinetic similar to normal controls (MST = 14.1 ± 1.2 days versus 13.6 ± 1.5 days). The prompt rejection of skin allografts by B cell deficient mice suggests that T cell activation and function are normal in vivo and that T cells alone are sufficient to reject allogeneic skin grafts. BMT was subsequently performed in presensitized μ MT mice 5 weeks after sensitization as well as in naïve μ MT mice. All naïve μ MT mice (n = 6) engrafted with 700 cGy TBI and 30 x 106 bone marrow cells, but none of the presensitized μ MT mice engrafted. Since humoral immunity is absent in sensitized μ MT mice, the increased barrier in these mice therefore must be mediated by the primed T cells. To further define the relative contribution of T cell subpopulations to alloresistance, we targeted these populations in vivo as preconditioning using monoclonal antibodies (mAb). Sensitized μ MT mice were treated with anti-α β-TCR, anti-CD8, anti-CD4 or anti-CD154 mAbs alone or in combination and 850 cGy of total body irradiation, then transplanted with untreated BALB/c donor bone marrow cells (Figure). Engraftment did not occur in the sensitized μ MT mice without mAb treatment, while nearly all animals engrafted with preconditioning with anti-α β-TCR alone, anti-CD8 plus anti-CD154, or anti-CD8 plus anti-CD4 (100%, 87.5%, and 100% respectively) and transplantation with 30 x 106 donor BM cells. Moreover, anti-α β-TCR preconditioning promoted engraftment in all sensitized μ MT mice with transplantation of as low as 15 x 106 BM cells. These data demonstrate that T cell mediated cellular immunity contributes to rejection in sensitized recipients, and that successful therapies to achieve allogeneic engraftment using nonmyeloablative conditioning in sensitized recipients will need to address both arms of the adaptive antigen-specific immune system: cellular and humoral. Figure Figure

scholarly journals H-2 effects on cell-cell interactions in the response to single non-H-2 alloantigens. I. Donor H-2D region control of H-7.1-immunogenicity and lack of restriction in vivo.

1977 ◽  
Vol 146 (5) ◽  
pp. 1346-1355 ◽  
Author(s):  
P J Wettstein ◽  
G Haughton ◽  
J A Frelinger
Keyword(s):  
Graft Rejection ◽  
Cell Interactions ◽  
Skin Grafts ◽  
Survival Times ◽  
Graft Donor ◽  
Effector Activity ◽  
Cytotoxic Effector ◽  
Cell Cell

Genes in the H-2 complex regulate the relative immunogenicity of the H-7.1 histocompatibility alloantigen, as measured by survival times of H-7.1-incompatible skin grafts in vivo. The gene controlling relative rejectability of H-7.1-incompatible grafts has been mapped to the H-2D region. H-7.1-incompatible skin grafts donated by H-2Db donors were rejected significantly more rapidly by H-2a/H-2b heterozygous recipients than similar H-7.1-incompatible grafts donated by H-2Dd donors. Further, there was absolutely no evidence of H-2 restriction in cytotoxic effector activity. In vivo cross-priming, as indicated by accelerated secondary graft rejection, was extensive. The efficiency of cross-priming was dependent upon the primary and secondary graft donor H-2 haplotypes.

Using skin transplants as early in vivo indicators for graft rejection in heart transplantation

2012 ◽  
Vol 60 (S 01) ◽  
Author(s):  
U Arunagirinathan ◽  
M Stubbendorff ◽  
T Deuse ◽  
X Hua ◽  
J Velden ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Graft Rejection

In Vivo Bioluminescence Imaging of Transplanted Islets and Early Detection of Graft Rejection

2006 ◽  
Vol 81 (10) ◽  
pp. 1421-1427 ◽  
Author(s):  
Xiaojuan Chen ◽  
Xiaomin Zhang ◽  
Courtney S. Larson ◽  
Marshall S. Baker ◽  
Dixon B. Kaufman
Keyword(s):  
Early Detection ◽  
Graft Rejection ◽  
Bioluminescence Imaging ◽  
In Vivo Bioluminescence Imaging

scholarly journals Exposure of ichnovirus particles to digitonin leads to enhanced infectivity and induces fusion from without in an in vitro model system

2007 ◽  
Vol 88 (11) ◽  
pp. 2977-2984 ◽  
Author(s):  
Don Stoltz ◽  
Renée Lapointe ◽  
Andrea Makkay ◽  
Michel Cusson
Keyword(s):  
Outer Membrane ◽  
In Vitro Model ◽  
Model System ◽  
Host Cells ◽  
Fusion Event ◽  
Susceptible Host ◽  
In Vitro Model System ◽  
Vitro Model

Unlike most viruses, the mature ichnovirus particle possesses two unit membrane envelopes. Following loss of the outer membrane in vivo, nucleocapsids are believed to gain entry into the cytosol via a membrane fusion event involving the inner membrane and the plasma membrane of susceptible host cells; accordingly, experimentally induced damage to the outer membrane might be expected to increase infectivity. Here, in an attempt to develop an in vitro model system for studying ichnovirus infection, we show that digitonin-induced disruption of the virion outer membrane not only increases infectivity, but also uncovers an activity not previously associated with any polydnavirus: fusion from without.

scholarly journals Induction of classical transplantation tolerance in the adult.

1989 ◽  
Vol 169 (3) ◽  
pp. 779-794 ◽  
Author(s):  
S X Qin ◽  
S Cobbold ◽  
R Benjamin ◽  
H Waldmann
Keyword(s):  
Bone Marrow ◽  
Transplantation Tolerance ◽  
Donor Strain ◽  
Skin Grafts ◽  
Donor Cells ◽  
Transplantation Antigens ◽  
Adult Bone ◽  
Tolerant State ◽  
Clonal Anergy

Transplantation tolerance across histoincompatibilities in multiple non-H-2 minors (B10.BR into CBA/Ca) and "minor" plus H-2D (B10.A into CBA/Ca) antigens has been achieved successfully by combined adult bone marrow transplantation and treatment with CD4 and CD8 mAbs. The tolerant state was confirmed by permanent acceptance of donor strain skin grafts, and in vitro unresponsiveness to donor cells. Tolerance was associated with partial donor chimerism to various degrees. Tolerance to minor transplantation antigens induced in this manner was restricted to recipient-type MHC. The possibility was raised that tolerance resulted, at least in part, from clonal anergy rather than deletion.

scholarly journals CELL-MEDIATED CYTOTOXICITY DURING REJECTION AND ENHANCEMENT OF ALLOGENEIC SKIN GRAFTS IN RATS

1972 ◽  
Vol 135 (6) ◽  
pp. 1301-1315 ◽  
Author(s):  
Hans-Hartmut Peter ◽  
Joseph D. Feldman
Keyword(s):  
Lymph Nodes ◽  
Thoracic Duct ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Skin Grafts ◽  
Peak Activity ◽  
Adult Rats ◽  
Background Levels

Cell-mediated cytotoxicity (CMC) in spleens and lymph nodes of allografted rats was determined by release of 51Cr from labeled target cells incubated with aggressor lymphoid cells. CMC was first detected in grafted adult rats on day 5, peaked on days 7 and 8, and declined rapidly to background levels by days 9 to 11. In allografted neonates and in cyclophosphamide-treated or neonatally thymectomized adults CMC was a fraction of that observed in normal adult rats. Enhancing antibodies deferred in vivo peak activity of CMC in allografted neonates for 3–4 days, and blocked in vitro the action of aggressor lymphocytes by binding to target cells. Enhancing antibodies had no effect on the cytotoxicity of aggressor cells, but horse antibodies to rat thoracic duct cells inhibited in vitro CMC of aggressor cells.

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