scholarly journals Colchicine allows prolonged survival of highly reactive renal allograft in the rat.

1993 ◽  
Vol 4 (6) ◽  
pp. 1294-1299
Author(s):  
D Ostermann ◽  
N Perico ◽  
O Imberti ◽  
C Barbui ◽  
M Bontempelli ◽  
...  
Keyword(s):  
Mixed Lymphocyte Culture ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocyte Culture ◽  
Brown Norway ◽  
Time Intervals ◽  
Term Survival ◽  
Kidney Allograft ◽  
Beneficial Effects ◽  
Histocompatibility Complex

Colchicine, with its immunosuppressive properties, has been used with beneficial effects in autoimmune diseases. Whether colchicine, by virtue of the above properties, could attenuate the process of kidney allograft rejection in the rat is investigated in this report. Untreated Lewis rats (N = 6) given an incompatible kidney allograft from Brown-Norway rats rejected the graft within 12 days. Colchicine at a daily ip dose of 40 (N = 6) or 10 (N = 4) micrograms/kg promoted long-term survival (> 170 days) of major histocompatibility complex-incompatible kidney grafts. Animals (N = 4) given 4 micrograms of colchicine per kilogram had a graft failure within 10 days. Experiments have also been performed to evaluate the effect of colchicine withdrawal at different time intervals from transplantation on subsequent allograft survival. Colchicine (40 micrograms/kg per day ip) was given for 12, 6, or 1 mo or for 15 days to an additional four groups of six animals each without any other immunosuppressants. The withdrawal of colchicine did confer long-term inhibition of the immune system in animals treated for at least 1 mo, as documented by a graft survival of more than 80 days. By contrast, those animals who discontinued colchicine after only 15 days of treatment had graft rejection within the next 8 days. Mixed lymphocyte culture experiments showed a significant (P < 0.01) reduction of the proliferation of peripheral blood lymphocytes taken from all groups of animals 30 days after colchicine withdrawal when challenged with Brown-Norway lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The role of nonclassical Fc receptor-associated, Ag-B antigens (Ia) in rat allograft enhancement.

1976 ◽  
Vol 143 (2) ◽  
pp. 405-421 ◽  
Author(s):  
J P Soulillou ◽  
C B Carpenter ◽  
A J d'Apice ◽  
T B Strom
Keyword(s):  
Fc Receptors ◽  
Mixed Lymphocyte Culture ◽  
Fc Receptor ◽  
Lymphocyte Culture ◽  
Brown Norway ◽  
Strain Specificity ◽  
Term Survival ◽  
Ia Antigens

The ability of a hyperimmune Lew anti-BN serum (HIS) to induce enhancement of (Lew/BN)F1 kidneys transplanted into Lew recipients was compared to that of the same antiserum that had been depleted of hemagglutinating anti-Ag-B antibodies by absorption with Brown-Norway (BN) RBC-absorbed sera (RAS) or platelet-absorbed sera (PAS). The RAS and PAS were as effective as the unabsorbed HIS in abrogating early rejection as assessed by renal function and promotion of long-term survival. The absorbed sera retained the capacity to block the mixed lymphocyte culture (MLC) between Lew and BN lymphocytes and to a lesser degree the MLC between Lew and BUF, WF, AUG, and ACI lymphocytes; however, strain specificity was clearly evident at high antiserum dilutions. Similarly, these absorbed sera retained the capacity to block the Fc receptor of BN lymphocytes, and this effect was completely strain specific. In contrast, hemagglutinating and cytotoxic antibodies eluted from platelets used for antiserum absorption did not react with Fc receptors as assessed by rabbit antisheep (IgG)-coated SRBC (EA) rosette formation. F(Ab')2 fragments of PAS also blocked EA rosettes. On the other hand, complement rosettes (EAC) were not inhibited by the HIS. The antibodies were therefore directed against the Fc receptor itself or a structure spatially or functionally closely related to it. Both the Fc receptors and the enhancing capacity of the antisera were strictly specific for the BN genotype. It is suggested that the anti-"Fc receptor" antibody could play an important role in the induction of enhancement by impairing host T-B collaboration as a result of its binding to graft allogeneic "Fc receptors" which appear to be analogous to the major histocompatibility complex (MHC)-coded Ia antigens of the mouse.

scholarly journals First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques

2020 ◽  
Vol 9 (11) ◽  
pp. 3694
Author(s):  
Iori Kisu ◽  
Yojiro Kato ◽  
Yohei Masugi ◽  
Hirohito Ishigaki ◽  
Yohei Yamada ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Antithymocyte Globulin ◽  
Nonhuman Primates ◽  
Humoral Rejection ◽  
Term Survival ◽  
Uterus Transplantation ◽  
Histocompatibility Complex ◽  
Cynomolgus Macaques ◽  
Donor Specific Antibodies

Delivery following uterus transplantation (UTx)—an approach for treating uterine factor infertility—has not been reported in nonhuman primate models. Here, six female major histocompatibility complex (MHC)-defined cynomolgus macaques that underwent allogeneic UTx were evaluated. Antithymocyte globulin and rituximab were administered to induce immunosuppression and a triple maintenance regimen was used. Menstruation resumed in all animals with long-term survival, except one, which was euthanized due to infusion associated adverse reaction to antithymocyte globulin. Donor-specific antibodies (DSA) were detected in cases 2, 4, and 5, while humoral rejection occurred in cases 4 and 5. Post-transplant lymphoproliferative disorder (PTLD) developed in cases 2 and 3. Pregnancy was attempted in cases 1, 2, and 3 but was achieved only in case 2, which had haploidentical donor and recipient MHCs. Pregnancy was achieved in case 2 after recovery from graft rejection coincident with DSA and PTLD. A cesarean section was performed at full-term. This is the first report of a successful livebirth following allogeneic UTx in nonhuman primates, although the delivery was achieved via UTx between a pair carrying haploidentical MHCs. Experimental data from nonhuman primates may provide important scientific knowledge needed to resolve unsolved clinical issues in UTx.

scholarly journals Antigens of human trophoblast. Effects of heterologous anti-trophoblast sera on lymphocyte responses in vitro.

1979 ◽  
Vol 149 (4) ◽  
pp. 824-836 ◽  
Author(s):  
J A McIntyre ◽  
W P Faulk
Keyword(s):  
Solid Phase ◽  
Human Lymphocytes ◽  
Complete Removal ◽  
Mixed Lymphocyte Culture ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocyte Culture ◽  
Reaction Products ◽  
Human Trophoblast ◽  
Total Inhibition

This report describes the inhibition of human mixed lymphocyte culture (MLC) reactions by rabbit antisera to intact and detergent solubilized, fractionated, human trophoblast membranes. Heat-inactivated antisera were passed through solid-phase immunoabsorption columns of normal human serum and extensively absorbed with human erythrocytes, lymphocytes and liver powder. Immunohistological experiments with these absorbed antisera showed that they reacted brilliantly with syncytiotrophoblast in cryostat sections of human but not baboon or monkey placentae, and not with other normal adult tissues including peripheral blood lymphocytes (PBL). Addition of these antisera to MLC reactions produced significant and reproducible suppression of responses without affecting cell viability. Absorption studies demonstrated complete removal of MLC inhibition and trophoblast membranes but not with PBL or suspensions of HEp-2 cells. Timed experiments showed that optimal inhibition occurred when the antisera were added between 2 and 6 h after culture initiation, and that little suppression was achieved after 18 h. Lymphocytes harvested from MLC reactions after 2 h showed that 3--5% of the cells reacted with PBL/liver-absorbed anti-trophoblast sera, and that unstimulated PBL were negative. Cultures of subhuman primate lymphocytes in the presence of heterologous antisera to human trophoblast membranes showed total inhibition of rhesus:human and human:rhesus MLC, and no suppression of baboon:human or human:baboon reactions, whereas human lymphocytes responded in an exagerated manner when stimulated by baboon cells. Modulated MLC responses to human, rhesus, or baboon lymphocytes, in the presence of anti-trophoblast sera indicate that the antisera recognize trophoblast cross-reactive lymphocytes antigens. We propose that these antigens are reaction products of cell-cell interactions, and that the nature of the antigens is determined by the specificity of the recognition signals which initiate the reaction.

scholarly journals CELL-MEDIATED LYMPHOLYSIS

1973 ◽  
Vol 137 (5) ◽  
pp. 1303-1309 ◽  
Author(s):  
Barbara J. Alter ◽  
Dolores J. Schendel ◽  
Marilyn L. Bach ◽  
Fritz H. Bach ◽  
Jan Klein ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Target Cell ◽  
Effector Cell ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Mouse Spleen ◽  
Spleen Cells ◽  
Histocompatibility Complex ◽  
Region Difference ◽  
Mediate Cell

The cell-mediated lympholytic capability of mouse spleen cells stimulated in mixed lymphocyte culture is related to the major histocompatibility complex genotype on target lymphocytes. The strain combinations AQR-B10. T(6R) and B10.A(4R)-B10.A(2R) that result in significant mixed lymphocyte culture activation do not mediate cell-mediated lympholysis on sensitizing target lymphocytes; serologically defined regions (H-2K and H-2D) are identical within each combination. H-2K or H-2D region disparity alone does not cause cell-mediated lympholysis. However after mixed lymphocyte culture activation as seen with B10.A-B10.T(6R), a target cell bearing only an H-2K region difference from the effector cell is sensitive to cell-mediated lympholysis. Likewise an H-2D region difference is an adequate target after mixed lymphocyte culture activation of the effector cell in the combination B10.A(2R)-B10.D2.

Low MHC class II variability in a marsupial

1994 ◽  
Vol 6 (6) ◽  
pp. 721 ◽  
Author(s):  
LM McKenzie ◽  
DW Cooper
Keyword(s):  
Genetic Variation ◽  
Mhc Class Ii ◽  
Fragment Length Polymorphism ◽  
Tammar Wallaby ◽  
Class Ii ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Macropus Eugenii ◽  
Histocompatibility Complex ◽  
Marsupial Species

The major histocompatibility complex (MHC) loci have been shown to be highly polymorphic in most eutherian ('placental') species studied. Several hypotheses have been advanced for the maintenance of this exceptional level of genetic variation, one of which suggests that it is necessary for successful eutherian reproduction. Marsupials (metatherians) and eutherians are the only two groups of viviparous mammals, but their modes of reproduction are quite distinct. Although marsupials have placentae, they are generally shorter lived and less invasive than in eutherians. Other investigations have shown that genetic variation at marsupial MHC class I loci is probably high. Weak or non-existent mixed lymphocyte culture responses previously reported in several marsupial species have suggested a lack of class II variation. Data have therefore been collected on the level of restriction fragment length polymorphism at MHC class II beta-chain encoding loci of a marsupial, Macropus eugenii (the tammar wallaby). This level is shown to be low, between the level of MHC variation found in cheetahs and a population of lions with a restricted genetic base. Attention is drawn to the need to collect more data on the level of class II variability in both eutherians and marsupials, and to the potential of marsupials for understanding the relation, if any, between mode of reproduction and MHC variability.

scholarly journals Bilirubin Can Induce Tolerance to Islet Allografts

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 762-768 ◽  
Author(s):  
Hongjun Wang ◽  
Soo Sun Lee ◽  
Carlotta Dell’Agnello ◽  
Vaja Tchipashvili ◽  
Joanna D’Avilla ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Heme Oxygenase 1 ◽  
Term Survival ◽  
Long Term Survival ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Beneficial Effects ◽  
Monocyte Chemoattractant Protein ◽  
Protective Genes

Induction of heme oxygenase-1 (HO-1) expression in recipients of allogeneic islets can lead to long-term survival (&gt;100 d) of those islets. We tested whether administration of bilirubin would substitute for the beneficial effects of HO-1 expression in islet transplantation. Administering bilirubin to the recipient (B6AF1) or incubating islets in a bilirubin-containing solution ex vivo led to long-term survival of allogeneic islets in a significant percentage of cases. In addition, administering bilirubin to only the donor frequently led to long-term survival of DBA/2 islets in B6AF1 recipients and significantly prolonged graft survival of BALB/c islets in C57BL/6 recipients. Donor treatment with bilirubin up-regulated mRNA expression of protective genes such as HO-1 and bcl-2 and suppressed proinflammatory and proapoptotic genes including monocyte chemoattractant protein-1 and caspase-3 and -8 in the islet grafts before transplantation. Furthermore, treatment of only the donor suppressed the expression of proinflammatory cytokines including TNF-α, inducible nitric oxide synthase, monocyte chemoattractant protein-1, and other proapoptotic and proinflammatory genes normally seen in the islets after transplantation. Donor treatment also reduced the number of macrophages that infiltrated the islet grafts in the recipients. Preincubation of βTC3 cells with bilirubin also protected the cells from lipid peroxidation. Our data suggests that the potent antioxidant and antiinflammatory actions of bilirubin may contribute to islet survival.

scholarly journals Cellular basis of neonatal induction of in vitro tolerance.

1976 ◽  
Vol 143 (6) ◽  
pp. 1545-1550 ◽  
Author(s):  
O J Kuperman ◽  
F H Bach
Keyword(s):  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Proliferative Phase ◽  
Helper Cells ◽  
Histocompatibility Complex ◽  
Induction Of Tolerance

The LD and SD antigens of the major histocompatibility complex subserve differential roles in the induction of the proliferative phase in mixed lymphocyte culture and in the cytotoxic reaction seen in cell-mediated lympholysis. The present study suggests that they also behave differently in the neonatal induction of tolerance. SD antigens appear to induce tolerance in the cytotoxic T lymphocytes very effectively, whereas LD antigens (or the cytotoxic targets coded by genes in the I and/or S regions) are relatively ineffective in this regard. LD antigens presented neonatally are effective at inducing tolerance in the proliferating helper cells.

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