摘要:

We studied the effects on survival of allogeneic skin grafts after treatment with hydrocortisone and/or inhibitors of prostaglandin synthesis: indomethacin and flufenamate. We found a marked synergistic effect of combined treatment with hydrocortisone and indomethacin or flufenamate. Neither hydrocortisone nor indomethacin or flufenamate, when given alone in relatively small doses, caused delayed graft rejection. However, when small doses of hydrocortisone were used in combination with flufenamate or indomethacin, the median survival time (MST) of allogeneic grafts was prolonged from 11.4 days to 20.9 and 23.8 days, respectively. Moreover, the increase in graft survival was comparable to that obtained by treatment with relatively high doses of azathioprine alone or combined with hydrocortisone. The finding of synergism between low doses of prostaglandin synthesis inhibitors and glucocorticoids in delaying graft rejection suggests that such treatment might provide a relatively safer means of achieving clinical immunosuppression than the high doses of steroids and azathioprine currently in use.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

In an attempt to determine whether culture conditions significantly influence autoreactivity, we tested the effects of fetal calf, syngeneic, and autogeneic serum with and without 2-mercaptoethanol on the murine self-reactive mixed lymphocyte culture. We used both unfractionated and T-enriched lymph node cells as responders and unfractionated and B-enriched irradiated spleen cells as stimulators in a primary mixed lymphocyte culture (MLC). Using unfractionated cells as responders to various stimulator cell populations, we found excellent allogeneic reactions in all media tested but minimal or no self-reactivity in syngeneic or autogeneic serum. When using T-enriched lymph node cells as responders, allogeneic reactivity was excellent but self-reactivity was present only in the cultures supplemented with fetal calf serum and 2-mercaptoethanol. The possibility that the substances in fetal calf serum and/or 2-mercaptoethanol may be needed to enhance minimal, but biologically relevant, self-reactivity is discussed, as well as the possibility that the culture supplements may be inducing “nonspecific” self-reactivity.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The Hh-1 (hybrid histocompatibility) effect in which F1hybrids with heterozygosity at the “D end” of the H-2 complex can reject parental grafts of the H-2bhaplotype was examined in four H-2 mutants wherein the mutation had affected the H-2Db, H-2Dd, or H-2Ldgenes. In bone marrow grafting experiments it was shown that two separate mutations affecting the H-2Dblocus did not affect the Hh-1 gene, suggesting that H-2Dband Hh-1 are probably two different genes. By contrast, experiments with two mutants, one affecting the H-2Ddand H-2Ldloci (B10.D2-H-2dml) and the other a loss mutation at the H-2Ldlocus (BALB/c-H-2dm2), demonstrate an alteration in the hybrid histocompatibility phenomenon and the presumption is made that the Hh-1 and H-2Ldlocus are identical. This presumption was supported by studies of Hh-1 using the EL4 tumor grafting model where marked differences in growth were noted in the (B10 BALB/ c)F1and (B10 BALB/c-H-2dm2)F1hybrids. By contrast, the functionally related natural killer (NK) phenomenon appeared to be the same in the BALB/c parent and dm2 mutant. Hybrid histocompatibility is a complex phenomenon but at this time we conclude that the H-2L locus is related to, if not identical to the Hh-1 gene but the H-2L locus is distinct from genes affecting the NK phenomenon.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Pretreatment of LEW rats with cyclosporin A (10 mg/ kg/day orally for 14 days) plus 10“ DA or (DA LEW)F1spleen lymphocytes on two occasions markedly prolonged the survival of subsequent DA renal allografts. The lymphocytotoxic antibody response was suppressed completely and renal biopsies showed a marked mono-nuclear cell infiltrate, but no other manifestations of rejection. Neither pretreatment with cyclosporin A alone nor pretreatment with splenic lymphocytes alone had any effect on the subsequent immune reaction. The immunosuppressive effect generated was dependent upon the dose of lymphocytes given, because pretreatment with 107cells on two occasions plus cyclosporin A was relatively ineffective at prolonging renal allograft survival. Pretreatment with 108(DA LEW)F1spleen cells plus cyclosporin A was also an effective combination, and ruled out the possibility that graft-versus-host (GVH) disease was responsible for the observed immu-nosuppression. This pretreatment protocol exhibited specificity in terms of rejection of a third-party (PVG) renal allograft, but not in terms of the lymphocytotoxic antibody response to this graft. Chimerism was not detected in long-term surviving animals using a51Cr release assay. When pretreatment was performed in LEW rats with a DA skin allograft plus cyclosporin A, a subsequent DA renal allograft was rejected normally, in combination with the skin graft. These findings suggest that clonal deletion had not occurred in these pretreatment protocols, but that a shift in immunoregulatory mechanisms was responsible for the long survival. There are possible clinical implications for the use of pretreatment schedules using donor antigen and cyclosporin A.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Monoclonal antibodies to human monomorphic class I and class II major histocompatibility complex (MHC) determinants have been used with immunofluorescence and immunoperoxidase techniques, to localize these antigens in normal human kidneys. HLA-DR antigen was located in the glomeruli (probably on endothelium as well as in the mesangium) and within the cells of cortical and medullary tubules. Dendritic cells in the renal inter-stitium stained brightly for the DR antigen and could be distinguished from the staining of capillary endothelium. The vascular endothelium of large vessels stained less densely for the HLA-DR antigen than for HLA-ABC antigens. The glomeruli stained intensely for the HLA-ABC antigens and diffuse staining of HLA-ABC antigens was also noted within renal tubular cells.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Strain B6.C-H-2bm12has a mutation in the I-A subregion of the mouse H-2 gene complex, which causes skin graft rejection, mixed lymphocyte reaction (MLR), and alterations in the expression of la antigens. The mutation affects the expression of Ia.3, 8, 9, 15, and 20 on normal spleen cells. When the spleen cells were stimulated with lipopolysaccharide (LPS), the expression of all la specificities were found except Ia.8. la molecules when internally labeled with3H-leucine can be precipitated with antisera directed against Ia.3, 9, 15, and 20, but not Ia.8. When F18 are made between the mutant bm12 and unrelated haplotypes, Ia.3, 9, 15 and 20 can be detected by microcytotoxic assay on normal spleen cells, but not Ia.8. These studies suggest: (1) The mutation affects either the amount of la molecules expressed on normal spleen cell surfaces or the molecule is anchored improperly in the cell surface such that it is not accessible for cytotoxicity and radioiodination. (2) Specificity Ia.8, which may be a combinatorial determinant, is absent in the mutant because of a structural alteration in one of the chains, probably the ft chain. (3) The mutation does not involve the Ae chain. The significance of this finding in relation to I region-mediated allorecognition and antigen presentation is discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The ability of pancreatic islets implanted into abdominal muscle to effect a recovery from streptozotocin-in-duced diabetes was compared with that of i.p. implants. Pancreases from 17 to 35 Lewis neonates were cultured for 6 days and placed in i.m. or i.p. sites in severely diabetic Lewis rats. Body weight, food and water intakes, urinary output, and 4-hr fasted plasma glucose levels returned to normal in both groups. Neither plasma insulin and glucose responses to intravenous glucose tolerance tests nor plasma glucose responses to oral glucose tolerance tests differed among i.m. or i.p. implant recipients and normal, age-matched controls, even after 1 week's prior challenge of insulin secretory capacity by a high sucrose diet. Plasma glucose levels were reduced after oral administration of tolbutamide in the three groups. Plasma glucagon levels of i.m. and i.p. implant recipients after a 4-hr fast or after an oral load of arginine were not significantly different from those of controls, although levels tended to be higher in the implant groups. Neither i.m. nor i.p. implant groups reverted to the diabetic state in the 10 months following pancreatic implantation. These findings validate the long-term efficacy of intramuscular implantation of cultured islets in reversing diabetes in inbred rats.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Transplants of isolated allogeneic pancreatic islets behave as if extremely immunogenic but vascularized segmental pancreatic allografts do not evoke such a rapid rejection of islet tissue. We have transplanted rat pancreatic islets as a vascularized graft by implanting isolated islets under the renal capsule of a syngeneic diabetic rat and, after successful reversal of diabetes, a composite graft of kidney and islets was transplanted into an allogeneic diabetic host. Cyclosporin A was used to suppress rejection of the allografts in doses that have previously been shown to completely suppress rejection of renal allografts and delay rejection of vascularized segmental pancreatic allografts. This strategy produced indefinite survival of the allogeneic isolated pancreatic islets.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

When viable B6AF1murine spleen cells were cultured in combination with heat-inactivated B10.D2 spleen cells under appropriate conditions, alloantigen-specific suppressor T cells (Ts) were generated. The optimal conditions for generation of specific Ts included a responder cell number of 2 to 4 106/ml, a high stimulator to responder ratio, the use of at least 30 min of heat treatment (45 C) of stimulator cells, and 6 or more days of culture.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We wish to report strong lymphocyte crossmatch incompatability attributable to anti-Leaantibody. The prospective renal transplant recipient was Le(a-b-) and her serum contained potent anti-Leaand anti-LebHantibodies. Despite the fact that we were able to demonstrate greater B lymphocyte than T lymphocyte Lewis(a+) an-tigenicity, this serum was capable of causing greater than 80% cytotoxicity of Le(a+) and Le(b+)O or A2whole lymphocyte populations. Antibody activity was completely inhibited by Lewis substance. This inhibition was specific and did not interfere with HLA antibody activity.

ISSN:0041-1337    

出版商:OVID    

年代:1981

数据来源: OVID