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PubMed1995

The regulation of expression of histocompatibility antigens on the cell surface; molecular genetic basis.

Histocompatibility antigens play a fundamental role in the immune functions by their polymorphic capture structure for binding exogenous and endogenous peptides and presenting them to the appropriate T and B cell receptors. The genetic background of the control of synthesis of the histocompatibility antigens is very complex including several loci controlling the wide polymorphic variation of class I and class II histocompatibility molecules and their regulation of expression. Most significant variability in the presence or absence of histocompatibility antigens could be observed during development, differentiation, and activation. The tissue-specific expression is influenced by pathological events such as malignant transformation, viral infection and genetic defectiveness as well. The research in the field of molecular genetics of the MHC in the last decade revealed, upstream of the coding genes of class I and class II molecules, a very complex regulatory machinery including a series of genes termed enhancer and promoter region. At the DNA level, various gene boxes and regulatory elements were discovered, which are activated by the binding of the appropriate histone proteins, cytokines or hormones responsible for the upregulation and downregulation of histocompatibility antigen expression. Regulation is mainly functioning at the transcriptional level, but other factors such as viral proteins, oncogenes, biomolecules, and physical effects take part, either indirectly or directly affecting the regulatory genes and DNA binding proteins. The increasing knowledge about the regulatory machinery may lead to the introduction of genetic manipulation, either experimental or clinical, with the aim of changing the expression of histocompatibility molecules on the cell surface in order to achieve normal or demanded immune functions.

Animals↗
PubMed1994

Histocompatibility differences and cardiac transplant tolerance produced by intrathymic pretreatment.

Control of cardiac transplant rejection without toxic immunosuppressive drugs remains an unreached goal. Our laboratory and others have shown that intrathymic inoculation of donor-specific allogeneic spleen cells can produce tolerance to a subsequent cardiac allograft. The present experiments were designed to investigate whether the degree of donor-recipient histoincompatibility influenced the efficacy of this technique. Four congeneic strains of rats with different degrees of histoincompatibility were studied. Heterotopic cardiac transplantation was done with the following congeneic strain combinations: DA donor into PVG recipient (full major histocompatibility complex and nonmajor histocompatibility complex incompatibility); PVG.RT1a donor into PVG recipient (full major histocompatibility complex incompatibility); PVG.RT1a donor into PVG.R1 recipient (partial major histocompatibility complex incompatibility). Prospective graft recipients underwent intraperitoneal injection of 1 ml antilymphocyte serum and intrathymic injection of 5 x 10(7) prospective donor spleen cells. Three weeks later, heterotopic cardiac transplantation was done with a heart from a donor of the same strain as that used to obtain splenocytes for intrathymic injection. Prolongation of graft survival was observed in pretreated recipients in all strain combinations but was greatest in recipients that differed from donors at fewer histocompatibility loci. Complete graft tolerance was not seen in strain combinations that included nonmajor histocompatibility complex incompatibilities. DA heart survival in PVG recipients was 50.6 days (p < 0.04 versus controls); PVG.RT1a graft survival in PVG hosts was 165.8 days (p < 0.02 versus control) and in PVG.R1 recipients 163.8 days (p < 0.02 versus controls) with four of five grafts in each group surviving indefinitely (more than 200 days).

Animals↗
PubMed1985

Complexity of minor histocompatibility loci.

Allografts can be rejected as a result of major histocompatibility antigen disparity or as a result of differences at any of a number of minor histocompatibility antigens. In many cases, rejection due to multiple minor histoincompatibility is as difficult to control as that induced by major histoincompatibility. Although an understanding of the molecular, biochemical, and functional parameters of the major histocompatibility loci and their products is increasing at an exponential rate, little is known about these same facets of minor histocompatibility loci and their products. It is generally accepted that minor histocompatibility loci in the murine model have a degree of polymorphism similar to that of H-2K or H-2D. This conclusion was based on typing alleles by the classic F1-skin graft test. Based on these allelic assignments, numerous unexpected findings of CTL specificity were made. Therefore, a systematic analysis was made comparing CTL specificity, F1-complementation, and allograft rejection. Based on these three parameters, the data presented using strains of mice that were bred to, and therefore presumed to, differ only at H-3 indicate that the antigen disparity of these congenic strains and the parental B10 strain as defined by CTL specificity and skin graft rejection is much more complex than originally described. One especially interesting chromosomal region is H-3/beta 2-microglobulin in the fifth linkage group of chromosome 2. Using CTL, ten specificities are defined, three of which appear to be specific for beta 2-microglobulin-A, -B, and -C. These findings raise the question of whether any minor histocompatibility locus is polymorphic or is instead a composite of multiple minor H-loci which are masquerading as a single locus.

Alleles↗
PubMed1998

Retinoic acid up-regulates the expression of major histocompatibility complex molecules and adhesion/costimulation molecules (specifically, intercellular adhesion molecule ICAM-1) in human cervical cancer.

OBJECTIVE: Retinoids are a class of compounds that are structurally related to vitamin A and have been found to be effective in the prevention and treatment of cervical cancer. To investigate whether enhanced immunogenicity might be responsible for such efficacy, we evaluated the effects of retinoic acid on the expression of major histocompatibility complex class I and class II and intercellular adhesion molecule ICAM-1 in human cervical carcinoma cell lines. STUDY DESIGN: The expression of surface antigens (major histocompatibility complex class I and class II and ICAM-1) was evaluated by fluorescence-activated cell sorter analysis in 3 human cervical carcinoma cell lines after exposure to therapeutic doses of retinoic acid. In addition, the effects on human leukocyte antigen class I messenger ribonucleic acid expression were also evaluated by Northern blot analysis after such treatment. RESULTS: CaSki, SiHa, and HT-3 cervical cancer cells expressed variable levels of major histocompatibility complex class I and ICAM-1 antigens, whereas class II surface antigens were not detectable. Exposure to therapeutic doses of retinoic acid were able to significantly increase the expression of major histocompatibility complex class I and ICAM-1 antigens in all the cell lines when compared with untreated tumor cells but were not able to induce the expression of class II surface human leukocyte antigens. Northern blot analysis showed that for major histocompatibility complex class I molecules such up-regulation was the result of an increased expression at the transcriptional level of major histocompatibility complex class I messenger ribonucleic acid. CONCLUSIONS: These data indicate that retinoic acid increases the expression of immunologically important surface antigens, suggesting that the efficacy of retinoic acid in the treatment of cervical cancer may be, at least in part, the result of immunologic modulation. Such findings support additional clinical research investigating the use of retinoids for the treatment of cervical cancer.

Blotting, Northern↗
PubMed1996

Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation.

BACKGROUND: Graft-versus-host disease (GVHD) can be a major complication of allogeneic bone marrow transplantation even when the donor and recipient are siblings and share identical major histocompatibility antigens. The explanation may be a mismatch of minor histocompatibility antigens. We previously characterized five minor histocompatibility antigens, HA-1, 2, 3, 4, and 5, that are recognized by T cells in association with the major histocompatibility antigens HLA-A1 an A2. METHODS: We collected peripheral-blood leukocytes from 148 bone marrow recipients and their sibling donors, who were genotypically HLA identical. Fifty pairs were positive for HLA-A1, 117 were positive for HLA-A2, and 19 were positive for both. The pairs were typed with cytotoxic-T-cell clones specific for minor histocompatibility antigens HA-1, 2, 3, 4, and 5. RESULTS: Mismatches of HA-3 were equally distributed among recipients in whom GVHD developed and those in whom it did not. By contrast, a mismatch of only HA-1 was significantly correlated with GVHD of grade II or higher (odds ratio, infinity; P = 0.02) in adults. One or more mismatches of HA-1, 2, 4, and 5 were also significantly associated with GVHD (odds ratio, infinity; P = 0.006) in adults. These associations were not observed in children. CONCLUSIONS: A mismatch of minor histocompatibility antigen HA-1 can cause GVHD in adult recipients of allogeneic bone marrow from HLA-identical donors. Prospective HA-1 typing may improve donor selection and identify recipients who are at high risk for GVHD.

Adolescent↗
PubMed1991

Expression and modulation of major histocompatibility antigens on murine primary brain tumor in vitro.

Lysis of tumor cells by activated cytotoxic lymphocytes requires their recognition of antigens associated with major histocompatibility complex molecules. The authors studied the constitutive expression of Class I and Class II major histocompatibility complex antigens on mouse brain-tumor cells and the capacity of different cytokines and cytokine combinations to alter this expression in vitro. Cells from the murine glioma 26 (GL26), glioma 261 (GL261), and ependymoblastoma A (EpA) cell lines were established in monolayer culture and treated for 48 hours with either alpha interferon, gamma interferon, tumor necrosis factor alpha, tumor necrosis factor alpha plus gamma interferon, or interleukin-2. They were then analyzed by flow cytometry for baseline and cytokine-altered major histocompatibility complex expression. All cell lines had a similar constitutive major histocompatibility complex pattern with low Class I antigen expression and no detectable Class II antigen expression. Alpha interferon substantially induced and up-regulated Class I antigen expression, but had no effect on Class II antigen expression. Gamma interferon also stimulated up-regulation of Class I antigen expression, generally doubling the anti-Class I antigen fluorescence of treated cells. Its effect on Class II antigen expression was more extensive. In the GL26 and GL261 cell lines the expression of Class II antigen determinants increased to 12 x and 14 x control values and as many as 75% of cells that had no detectable constitutive expression of Class II antigen expressed this antigen after priming with gamma interferon. The addition of tumor necrosis factor alpha to gamma interferon further increased Class II antigen expression on EpA tumor cells only. Interleukin-2 and tumor necrosis factor alpha alone had no effect on Class I or Class II antigen expression of any cell lines. It is concluded that Class I and Class II antigen expression in mouse glioma cell lines is induced and enhanced after treatment with certain cytokines in vitro. Use of these cell lines to create in situ primary brain tumors in C57BL/6 mice should provide an excellent animal system to study major histocompatibility complex modulation in brain tumor cells and to examine the potential impact of major histocompatibility complex up-regulation on the response of brain tumors to immunotherapy.

Animals↗
PubMed1987

Effect of maternal-fetal histoincompatibility on the weight of the feto-placental unit in mice: the role of minor histocompatibility antigens.

Female mice from four congenic strains were bred to males of the same four strains to determine the effect of maternal-fetal disparity at major histocompatibility complex (MHC) and the effect of non-MHC minor histocompatibility antigens on the weight of the feto-placental unit. An increase in feto-placental weights was found in all three of the four strains that could be evaluated when mother and fetus differed at multiple minor histocompatibility loci, irrespective of whether disparity at the MHC was present. No increase in feto-placental weights was found when mother and fetus differed at the MHC alone. The fact that these results were found in all strains studied suggests that the effect of maternal-fetal disparity at multiple minor histocompatibility antigens (minor HA) on the weight of the feto-placental unit is biologically significant. We conclude that if the increase in weight of the feto-placental unit results from immunostimulation, then minor histocompatibility antigens are the primary target of the maternal immune response to the histocompatibility antigens of the fetus.

Animals↗
PubMedDate not supplied

Expression of major histocompatibility antigens and vascular adhesion molecules on human cardiac allografts preserved in University of Wisconsin solution.

The impact of cold storage of cardiac allografts on expression of major histocompatibility complex antigens and vascular adhesion molecules is not known. We obtained serial endomyocardial biopsy specimens at harvest, on implantation, and approximately 15 minutes after reperfusion from six consecutive human cardiac allografts stored in University of Wisconsin solution. Cold ischemia time was 187 +/- 45 minutes. A fourth endomyocardial biopsy specimen was obtained from the recipients of cardiac allografts 1 week after operation. Expression of major histocompatibility complex antigens and vascular adhesion molecules was studied by immunohistochemistry. The intensity was scored blindly by a semiquantitative method. On vascular endothelial cells, the expression of major histocompatibility complex class I and II antigens was strong; ICAM-1 expression was moderate, and expression of VCAM-1 and ELAM-1 was weak to absent. The expression of these antigens on vascular endothelial cells did not change in sequential biopsy specimens. The expression of major histocompatibility complex class I antigens on myocardial cells was weak and remained unchanged. Myocardial cells did not express major histocompatibility complex class II antigens, ICAM-1, VCAM-1, or ELAM-1 on serial examinations. During cold storage of cardiac allografts in University of Wisconsin solution, the expression of major histocompatibility complex antigens and vascular adhesion molecules on endothelial cells and myocardial cells remains unchanged.

Adenosine↗
PubMed1988

Histocompatibility antigen changes associated with pink-eyed dilute (p) mutations.

The tight linkage between the H-4 histocompatibility locus and the pink-eyed dilute (p) locus raises the possibility that a single gene is responsible for both a histocompatibility antigen and coat color phenotype. To examine this possibility, we have investigated the effects of a spontaneous coat color mutation, pink-eyed unstable (pun), which occurred at the p locus in the C57BL/6J inbred strain, on histocompatibility antigen phenotype. Skin grafts were transplanted from two independently maintained B6-pun substrains to coisogenic, wild-type C57BL/6 recipients; graft rejection uniformly commenced at 6-7 weeks but did not culminate in complete graft destruction as observed in other cases of "crisis" rejection. Neither the onset of rejection time nor the intensity of rejection could be accelerated by introducing new H-2 haplotypes into the wild-type recipients. These results suggested that the pun allele was associated with a histocompatibility antigen not shared with C57BL/6. The pun allele is characterized by a relatively high frequency of reversion to wild-type. Therefore, skin grafts from B6-pun donors were transplanted to homozygous, revertant (+/+) recipients which were subline-matched with the donors; these grafts underwent crisis rejection with the same time of onset of rejection as observed with C57BL/6 recipients. These observations indicate that a new histocompatibility antigen is associated with the pun mutation and is lost upon reversion to wild type; this association is the first demonstration of a link between histocompatibility and coat color phenotypes.

Animals↗
PubMed1996

Effects of ursodeoxycholic acid and chenodeoxycholic acid on major histocompatibility complex class I gene expression.

We investigated the effect of ursodeoxycholic acid on major histocompatibility complex class I gene expression in cultured human hepatoma cells. Ursodeoxycholic acid, which is now being used for the treatment of various autoimmune liver diseases, paradoxically increased the mRNA level of major histocompatibility complex class I. However, endogenous bile acids, for example, chenodeoxycholic acid, increased major histocompatibility complex class I mRNA expression more strongly compared with ursodeoxycholic acid. Concerning the interplay between ursodeoxycholic and chenodeoxycholic acids, these bile acids additively induced major histocompatibility complex class I mRNA expression. In contrast, when the total concentration of ursodeoxycholic and chenodeoxycholic acids was kept constant, the expression of major histocompatibility complex class I mRNA appeared to decrease in a dose-dependent manner with an increasing ratio of ursodeoxycholic acid. These findings indicate that the beneficial action of ursodeoxycholic acid may be related to this relative decrease in major histocompatibility complex class I gene expression.

Blotting, Northern↗
PubMed1990

Identification of classical minor histocompatibility antigen as cell-derived peptide.

Histocompatibility antigens expressed on tissue grafted between individuals are recognized by host T cells, which reject the graft. The major histocompatibility complex (MHC) antigens have been identified on the molecular level, whereas the molecules representing the remaining ones, the minor histocompatibility antigens, are unknown, apart from some exceptions. The cytotoxic T lymphocyte (CTL) response against minor histocompatibility antigens shares many aspects with that against virus-infected cells. Virus-specific CTL recognize peptides derived from viral proteins produced in the infected cell. These peptides are presented by MHC class I molecules, as indicated by functional and crystallographic data. By analogy, minor histocompatibility antigens have been postulated to be peptides derived from normal cellular proteins presented by MHC class I molecules. Here we report that peptides derived from normal cellular proteins can indeed be recognized by CTL raised in the classical minor histoincompatible mouse strain combination, C57BL/6 against BALB.B. Thus, we have proven the above postulate, and isolated one of the minor histocompatibility molecules elusive for several decades.

Animals↗
PubMed2001

Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease.

Adoptive transfer of T cells reactive to minor histocompatibility antigens has the unmatched ability to eradicate malignant hematopoietic cells. Unfortunately, its use is hampered by the associated graft-versus-host disease. The critical issue of a possible dissociation of the antileukemic effect and graft-versus-host disease by targeting specific minor histocompatibility antigens remains unresolved because of the unknown nature and number of minor histocompatibility antigens necessary or sufficient to elicit anti-leukemic activity and graft-versus-host disease. We found that injection of T lymphocytes primed against a single major histocompatibility complex class I-restricted immunodominant minor histocompatibility antigen (B6dom1) caused no graft-versus-host disease but produced a curative anti-leukemic response. Avoidance of graft-versus-host disease required that no other host-reactive T cells be co-injected with T cells primed with B6dom1. Here we show that effective and non-toxic immunotherapy of hematologic malignancies can be achieved by targeting a single immunodominant minor histocompatibility antigen.

Adoptive Transfer↗
PubMed1995

In vitro recall of proliferative and cytolytic responses to minor histocompatibility antigens by dendritic cell enriched canine peripheral blood mononuclear cells.

It is difficult in vitro to demonstrate existent in vivo sensitization of dogs and humans to minor histocompatibility antigens. Using conventional one-way mixed leukocyte culture, when sensitized blood cells are stimulated with MHC antigen-matched sibling PBMC bearing the minor histocompatibility antigens, there is usually no proliferative or cytotoxic response detected. We reported previously that 0 of 17 dogs sensitized by transfusion of dog leukocyte antigen-identical littermate blood had proliferative responses in mixed leukocyte culture when unfractionated sibling PBMC were used as stimulator cells. We reasoned that this result might be due to the inability of unfractionated PBMC to efficiently present minor histocompatibility antigens to the in vivo-primed T cells, a function thought best performed by dendritic cells. When we used a low buoyant density Percoll fraction of canine PBMC, shown previously to be enriched in dendritic cells, as stimulator cells, we were able to generate cytotoxic and/or proliferative responses in mixed leukocyte culture in all 5 dogs that had been sensitized to minor histocompatibility antigens by transfusions of dog leukocyte antigen-identical sibling littermate blood. By contrast, using unfractionated PBMC as stimulator cells, we found evidence of sensitization in only 1 of the 5 dogs. These data support the concept that the presentation of minor histocompatibility antigens, in contrast to major histocompatibility antigens, to the immune system may be restricted to a subpopulation of professional APC.

Animals↗
PubMed2005

Role of major histocompatibility complex class I molecules in autoimmune myositis.

PURPOSE OF REVIEW: Recent work has continued to clarify the role of major histocompatibility complex class I in the pathogenesis of autoimmune myositis. In the past year, several new observations have been made in this area. This review describes these findings and discusses their relevance to the pathogenesis of autoimmune myositis. RECENT FINDINGS: Recent studies have confirmed earlier observations of the up-regulation of major histocompatibility complex class I antigens in myositis. In particular, a recent study has strengthened the conclusion that major histocompatibility complex class I expression is highly specific to inflammatory myopathies and may be of diagnostic value. Two new studies have indicated that endoplasmic reticulum stress response pathway (the endoplasmic reticulum overload [NF-kB] and unfolded protein response [GRP78]) are highly activated in patients with myositis. One study using transgenic mice has further indicated that abnormal accumulation of major histocompatibility complex class I in the endoplasmic reticulum of muscle may be responsible for the initiation of this endoplasmic reticulum stress response. Furthermore, studies of normal muscle cells have shown that endoplasmic reticulum stress also plays an important role in skeletal muscle development. Investigations of autoantigen expression in myositis biopsies have revealed that regenerating muscle cells express high levels of autoantigens and major histocompatibility complex class I, indicating that these cells are the targets of cytotoxic T-cell attack and may participate in the initiation of a myositis-specific autoimmune response. SUMMARY: Defining the role of major histocompatibility complex class I in autoimmune myositis may be useful not only for diagnosis of this group of diseases but also for therapeutic opportunities for these difficult disorders.

Animals↗
PubMed1999

Primary cortical glial reaction versus secondary thalamic glial response in the excitotoxically injured young brain: microglial/macrophage response and major histocompatibility complex class I and II expression.

The excitatory amino acid analog, N-methyl-D-aspartate, was injected intracortically into nine-day-old rats. Resulting axon-sparing lesions in the developing sensorimotor cortex, which secondarily affect thalamic neurons that become deprived of cortical targets, provide an experimental model for the study of the glial response in distantly affected areas. The microglial/macrophage response was studied using tomato lectin histochemistry and major histocompatibility complex I and II immunocytochemistry. Blood-brain barrier integrity was evaluated. In the cortical lesion site, where blood-brain barrier breakdown occurs, the rapid microglial response was restricted to the degenerating area. Microglial changes were first seen at 4 h post-injection, peaking at days 3-5. Reactive microglia changed morphology, increased tomato lectin binding and expressed major histocompatibility complex I. Additionally, some cells expressed major histocompatibility complex II. In the secondarily affected thalamus, the microglial response was not as pronounced as in the cortex, was first seen at 10 h post-injection and peaked at days 3-5. Reactive microglia showed a bushy morphology, were intensely lectin positive and expressed major histocompatibility complex I. The exceptional response of the nine-day-old brain to cortical lesions makes this model an interesting tool for studying the implications of microglial major histocompatibility factor expression in still enigmatic processes such as wound healing and plasticity.

Animals↗
PubMed1999

Cutting edge: alloimmune responses against major and minor histocompatibility antigens: distinct division kinetics and requirement for CD28 costimulation.

Comparative study of alloimmune responses against major and minor histocompatibility Ags has been limited by the lack of suitable assays. Here, we use a bioassay that permits tracking of alloreactive CD4+ T cell populations as they proliferate in response to major or minor histocompatibility Ags in vivo. Division of alloreactive CD4+ T cells proceeded more rapidly in response to major histocompatibility Ags than minor Ags, although CD4+ T cells alloreactive to minor Ags had a similar capacity to divide successively up to eight times after stimulation. Allorecognition of minor histocompatibility Ags was highly dependent on CD28 costimulation, with the frequency of CD4+ T cells proliferating in response to minor Ags in the absence of CD28 costimulation reduced up to 20-fold. These findings highlight differences in signaling processes that lead to allorecognition of major and minor histocompatibility Ags and have implications on the design of interventions aimed at abrogating these responses.

Animals↗
PubMed1996

Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat: virus-induced expression of major histocompatibility complex class II antigens.

BACKGROUND: Cytomegalovirus infection is considered a major complication after lung and heart-lung transplantation because it can trigger acute and chronic rejection. The potential mechanisms of lung transplant rejection induced by viral infection include the upregulation of expression of major histocompatibility complex antigens. To address this question, a model of rat cytomegalovirus infection and acute lung transplant rejection was established. METHODS: Lewis inbred strain rats received syngeneic (n = 25) or allogeneic (Brown-Norway inbred rat strain, n = 38) orthotopic left-side lung transplants. Triple-drug immunosuppression with cyclosporin A, methylprednisolone, and azathioprine was given from postoperative days 1 through 10. Rat cytomegalovirus was inoculated intraperitoneally on postoperative day 3. Two control groups, those infected with cytomegalovirus (n = 15) and those without rat cytomegalovirus infection (n = 6) were treated with identical immunosuppressive regimens. Animals were sacrificed on postoperative days 11, 15, 18, 20, and 25. The salivary glands and both lungs were removed for pathologic and immunohistochemical investigations. RESULTS: All animals inoculated with rat cytomegalovirus developed systemic viral infection on or after postoperative day 11, as confirmed by an assay of plaque-forming units and immunohistologic examination. Cytomegalovirus-induced expression of major histocompatibility complex class II antigens on vascular endothelial cells was seen in the nontransplanted lungs of rats, but no major histocompatibility complex class II antigens were detected on noninfected, nontransplanted lungs. Cytomegalovirus infection also was found to enhance major histocompatibility complex class II antigen expression on pneumocytes and leukocytes in rats. Acute rejection occurred in allogeneic transplants from postoperative days 15 through 25. The expression of class II antigens on endothelial cells, pneumocytes, and leukocytes was further enhanced during the course of allograft rejection in the cytomegalovirus-infected rats compared with the noninfected controls. In cytomegalovirus-positive rats, the rejection grade was higher than that in cytomegalovirus-negative rats on postoperative days 15 through 18. CONCLUSIONS: Our results indicate that cytomegalovirus induces and enhances the expression of major histocompatibility complex class II antigens on endothelial cells, pneumocytes and leukocytes. Upregulation by cytomegalovirus infection may trigger or promote acute rejection by alloantigenic T-lymphocyte stimulation after lung transplantation. By this mechanism it may strongly influence the long-term course of lung transplant rejection.

Acute Disease↗
PubMedDate not supplied

The relative roles of major and minor histocompatibility antigens in the induction of immunologic unresponsiveness by blood transfusion.

Renal allograft survival may be prolonged indefinitely in some strains of rats following preoperative transfusion with whole blood from the organ donor. Similarly donor-specific transfusion results in a reduction in the proliferative response of lymph node (LN) white cells (WBCs) to donor-specific stimulators in mixed-lymphocyte culture (MLC). To determine the relative roles of major and minor histocompatibility antigens in the depression of the proliferative response, in vitro lymphocyte proliferation assays were performed using congenic rat strains as blood donors. Unidirectional MLCs were set up between haplotype-disparate responder and stimulator LN cells, in cases in which the responding cells had been harvested from rats transfused with blood that shared either some, all, or none of the major histocompatibility complex genes with the stimulator strain. The proliferative response of LN cells harvested from rats transfused with blood sharing major (class I or II) or minor antigens, or both, with the in vitro stimulator cells was significantly less than the response of cells harvested from nontransfused controls. No single-locus product was more or less effective than whole blood in depressing cell proliferation. These data suggest that the beneficial effect of preoperative random blood transfusions observed in clinical transplantation may arise from the fortuitous sharing by the blood donor and the subsequent organ donor of not only a single major histocompatibility antigen but also of minor histocompatibility antigens.

Animals↗