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Results for “immune suppression”

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At least 19 recordsLinked to original sources
PubMed1976

Genetic control of specific immune suppression. III. Mapping of H-2 complex complementing genes controlling immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).

Earlier studies from our laboratory demonstrated that the terpolymer of L-glutamic acid, L-alanine, and L-tyrpsine (GAT) stimulated the development of T cells capable of specifically suppressing the antibody responses in vivo and in vitro of nonresponder strains (bearing the H-2(s), H-2(q), and H-2(p) haplotypes) to GAT complexed with an immunogenic carrier, methylated bovine serum albumin, MBSA (1,2). We then extended these findings to another antigen, the copolymer of L-glutamic acid and L-tyrosine (GT). None of 19 inbred or congenic resistant mouse strains developed antibody responses to GT after immunization with this synthetic polypeptide in adjuvants. All the strains investigated, however, developed IgG plaque-forming cells (PFC) primary responses to GT complexed with MBSA (3). This permitted us to determine that: (a) preimmunization with GT suppressed the response to GT-MBSA in certain but not in all strains; (b) the suppression could be transferred by thymocytes and spleen cells from GT-primed animals; (c) the development of GT-specific suppressor cells is under dominant control of H-2- linked gene(s) which have been designated specific immune suppressor genes (Is genes); (d) the Is genes are antigen specific since GAT-MBSA responses are suppressed by GAT in strains carrying the H-2(q) haplotype, while GT-MBSA responses are not suppressed by the related polymer GT in these same strains (3,4). The experiments reported in this study map the Is genes responsible for GT-specific suppression within the H-2 complex. The data indicate that the K and D loci are not concerned with GT-specific suppression, and that this phenomenon is controlled by complementing or interacting genes which map on either side of cross-over events between the IB and IC subregions.

Animals↗
PubMed1975

Influence of antibody-mediated immune suppression on clinical, viral, and immune responses to swine influenza infection.

Antibody-mediated immune suppression occurred when newborn pigs with naturally acquired passive antibody were exposed to seine influenza virus. Frequency and relative ease of recovery of virus from nasal secretions were inversely related to the concentration of specific passive antibody existing at time of exposure. Severe overt respiratory signs during the acute stages of the disease were observed only in pigs with low passive antibody concentrations. The concentration of passive antibody at the time of exposure determined the immune status of the pig during the convalescent stage of disease. Infection could occur in the presence of high passive antibody concentrations, but the pig was not immunologically stimulated. Reexposure after the decay of passive antibody produced primary immune respone, severe clinical reinfection, and recovery of virus from nasal secretions for a period of time similar to that seen in pigs having their first exposure. Infection of newborn pigs with low passive antibody concentrations led to immunologic priming. A second exposure to virus produced a secondary immune response, mild clinical disease, and shortened time during which virus was recovered from nasal secretions. The relevance of these studies for the practice of vaccination or infections of the dam before parturition so that the neonate will have specific passive immunity is discussed.

Aerosols↗
PubMed2026

Integrated Functional Characterization of Hemileia vastatrix Effector Candidates Reveals Coordinated Immune Suppression, Sequential Deployment and Compartment-Specific Targeting.

Coffee leaf rust, caused by the obligate biotrophic fungus Hemileia vastatrix, remains the most destructive disease of coffee worldwide. Although genomic and transcriptomic studies have identified a large number of candidate effectors, experimental evidence supporting their biological roles during infection remains limited. Here, we integrated functional assays, temporal expression profiling during coffee infection and subcellular localization analyses to investigate the biological properties of 44 H. vastatrix effector candidates (HvECs). Using the Pseudomonas fluorescens EtHAn effector delivery system in Nicotiana benthamiana, 15 HvECs consistently suppressed pattern-triggered immunity (PTI), indicating that immune suppression is a widespread property among the H. vastatrix effector repertoire, as assessed in this heterologous system. Five HvECs also attenuated AvrB-triggered effector-triggered immunity (ETI), and three suppressed both PTI and ETI, suggesting that a subset of HvECs targets conserved regulatory nodes shared by these interconnected immune pathways. Temporal expression profiling revealed sequential deployment of HvECs throughout infection, with distinct subsets predominating during pre-biotrophic development, host penetration or biotrophic colonization, consistent with stage-specific functions during fungal pathogenesis. Subcellular localization analyses further showed that HvECs preferentially accumulated in the nucleus or chloroplasts, compartments known as central hubs of plant immune regulation. This study provides the most comprehensive functional characterization of H. vastatrix effector candidates to date, establishes a biologically informed framework for prioritizing candidates for future identification of avirulence determinants recognized by SH resistance genes, and advances our understanding of how the coffee rust fungus orchestrates immune suppression across time and cellular space during pathogenesis.

Nicotiana↗
PubMed1978

Improved immune-suppression techniques for the exongrafting of human tumours.

The transplantability of a xenografted human adenocarcinoma has been examined in mice that had been immune-suppressed by thymectomy and whole-body irradiation and the results have been compared with transplantation into athymic (nude) mice. Two alternative techniques were used to prevent marrow failure following whole-body irradiation: reconstituting the animals with a marrow graft, or protecting them by an injection of cytosine arabinoside (Ara-C) 2 days before the irradiation. The results show that the Ara-C-prepared mice were more receptive to transplantation than marrow-grafted or nude mice, and they were the only animals that developed regional metastases from implanted xenografts. Some recovery of immunity occurred in both types of immune-suppressed mice, which was evident more than 5 weeks after immune-suppression and which was more marked in females than in males. It was concluded that the immune-suppressed mice were superior to nude mice for short-term experiments but they may be less satisfactory for long-term experiments.

Adenocarcinoma↗
PubMed1979

Prognistic relevance of radiation induced immune suppression in breast carcinoma.

The extent of radiation induced immune suppression was analysed in 100 patients with carcinoma of the breast. The relative changes of lymphocyte counts and stimulations by PHA and PPD were similar in patients who differed with regard to age, size of tumour and its malignancy grade or axillary node condition. Moreover, no difference in the degree of radiation induced immune suppression existed between patients who developed recurrent disease and those who remained free of disease during a follow-up period of 4 1/2 to 7 years.

Breast Neoplasms↗
PubMed1978

Immune suppression of hematopoiesis.

Recent evidence suggests that immune mechanisms can injure proliferating hematopoietic precursor cells in the bone marrow. These may involve either humoral antibody or cell-mediated cytotoxic mechanisms. Immune injury can result in a variety of bone marrow failure syndromes. Immunologically induced abnormalities or blood cell production may be restricted to a single series, such as erythrocyte or granulocyte precursors, or may involve several hematopoietic lines; clinical manifestations reflect the cell line or lines that are injured. Immune suppression of hematopoiesis has now been described in pure red cell aplasia, immune panleukopenia, systemic lupus erythematosus, atypical cases of aplastic anemia and miscellaneous other hematologic diseases.

Agranulocytosis↗
PubMed1976

Analysis of the cross-reactive immune suppression induced by the random copolymers L-glutamic acid50-L-tyrosine50 (GT), L-glutamic acid60-L-alanine40 and L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

Cross-reactivity in the induction of immune suppression by the structurally related polymers of L-glutamic acid, L-alanine, and/or L-tyrosine (GAT, GA, GT) was studied. SJL (H-2S) and DBA/1 (H-2q) mice are nonresponders to GAT and GT, whereas SJL, but not DBA/1 responds to GA. Both strains respond to these polymers when complexed to the immunogenic carrier methylated bovine serum albumin (MBSA). Preimmunization with GA suppresses GA-MBSA as well as GAT-MBSA and GT-MBSA plaque-forming cell (PFC) responses in DBA/1 mice. Likewise, GAT suppresses GAT-MBSA and GA (SJL) and GA-MBSA (DBA/1) PFC responses in both strains while being totally ineffective on GT-MBSA responses. GT preimmunization suppressed GA, GAT-MBSA, and GT-MBSA PFC responses in SJL but not DBA/1 responses. This study demonstrates that cross-reactive immune suppression does not follow predictable patterns based upon cross-reactivity of specific antibodies and that cross-suppression is not reciprocal.

Alanine↗
PubMed1975

[Panarteritis nodosa-Special aspects of glucocorticoid and immune suppressive therapy (author's transl)].

Report dealing with the clinical and pathoanatomical course as well as the autopsy findings in a 54 year old female suffering from panarteritis nodosa. Onset of the illness with polyneuritis and arthralgia. One year later diagnosis of panarteritis nodosa verified by muscle biopsy. Deterioration of the disease leading to the development of peripheral gangrene could not be prevented in spite of intensive therapy with steroids, immune suppressive agents, digitalis and antihypertensive drugs. Death 4 years later by myocardial infarction. Autopsy revealed generalized healed panarteritis nodosa with scarring and obliteration of vessels. A short description of the symptoms of the disease is given and the efficacy of the therapy with steroids and immune suppressive drugs is discussed from the clinical as well as the pathoanatomical point of view. Immunopathologic mechanisms are considered to be the responsible factors for pathogenesis.

Antihypertensive Agents↗
PubMed2026

Single-cell profiling reveals a novel CAF subpopulation linking stromal heterogeneity to immune suppression in breast cancer subtypes.

BACKGROUND: The tumor microenvironment critically influences breast cancer (BC) progression, immune surveillance, and therapeutic response. Cancer-associated fibroblasts (CAFs), a heterogeneous stromal population, are key regulators of these processes, yet their subtype-specific contributions in BC remain insufficiently defined. METHODS: We integrated three single-cell RNA sequencing datasets from 29 BC patients to characterize stromal populations. Bulk RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed to assess correlations between CAF subsets and immune infiltration. Gene signatures were derived to identify subtype-specific CAF-immune interactions, prognostic markers, and potential predictors of chemotherapy response. RESULTS: Three conserved stromal populations (iCAFs, myCAFs, and pericytes) were identified, along with a previously unrecognized subset, the cluster 3 (CL3) CAF-like cells, referred as metabolic stressed CAF (msCAF). msCAF cells displayed transcriptional programs associated with antigen presentation, stress response, glycolysis, and extracellular matrix remodeling. Their abundance was inversely correlated with T-cell infiltration and function, in a subtype-specific manner: triple negative breast cancer (TNBC) was enriched for msCAFs in immune-infiltrated but functionally constrained microenvironments, whereas Luminal A tumors exhibited weaker immune infiltration with heterogeneous CAF-immune associations. msCAFs were characterized by a conserved gene signature (HLA-A, HLA-C, IL32, EMP3) and subtype-specific genes related to T-cell exhaustion. Several genes demonstrated prognostic relevance with distinct patterns in Luminal A (IER3, TIMP1, TBX3, SEC61G) and TNBC (ADM, C4orf3, LDHA) tumors, as well as shared biomarkers (FN1, LOXL2, P4HA1). Multiple msCAF genes also predicted chemotherapy response, suggesting utility as treatment stratification biomarkers. CONCLUSION: msCAFs represent a clinically relevant CAF subset that drives immune suppression, impacts subtype-specific prognosis, and influences therapy response in BC. These findings highlight msCAFs as promising targets for enhancing immunotherapy and personalizing treatment strategies.

Humans↗
PubMed1979

Growth kinetics of a rat mammary tumour transplanted into immune-suppressed mice.

The growth kinetics of a transplanted rat mammary tumour and its xenografts in immune-suppressed mice were studied using the technique of labelled mitoses. Growth of the tumour in rats was regular and uniform but when transplanted into mice the growth of the implants was irregular and generally slower. The second passage tumours in mice showed rapid and regular growth with a volume doubling time approximately half that for the tumours in the rat. Values for the G1 phase duration, intermitotic time and growth fraction were greater for the tumours in the mouse although the data for the first passage in mice were difficult to interpret. The kinetic changes between the rat and mouse hosts primarily reflect a large and variable amount of cell loss from the first passage xenografts in the mouse, with adaptation by the second passage towards reduced cell loss.

Animals↗
PubMed1979

A lung colony clonogenic cell assay for human malignant melanoma in immune-suppressed mice and its use to determine chemosensitivity, radiosensitivity and the relationship between tumour size and response to therapy.

A lung colony assay for clonogenic cells of human tumours in immune-suppressed mice is presented. The assay was used to determine the chemosensitivity of two malignant melanomas. One tumour reproduced the spectrum of chemosensitivity associated clinically with three cytotoxic agents. The other melanoma reproduced the chemosensitivity demonstrated in the patient from whom the tumour was biopsied. The importance of tumour size as a determinant of response to melphalan was investigated and the clonogenic cell survival in smaller tumours was found to be slightly but significantly lower than in larger tumours. An invesitgation of the importance of size as a determinant of response to radiotherapy demonstrated that 0.5-mm diameter tumour nodules were significantly more sensitive to irradiation than 2-cm diameter nodules. The hypoxic fraction of the larger tumours was 65 per cent, which is higher than that reported for experimental animal tumours or a human pancreatic tumour. This could be a factor in the clinical radioresistance of malignant melanoma.

Animals↗
PubMed1978

An in vitro colony assay for human tumours grown in immune-suppressed mice and treated in vivo with cytotoxic agents.

An in vitro agar colony technique has been developed for the growth of tumour cells taken directly from human tumours grown in immune-suppressed mice. The novel feature of the technique is the addition of a replenishable liquid phase which permits the maintenance of relatively slowly growing cells. A number of different xenografted tumours have been cultured successfully in this system, with red blood cells added to the agar and using 5% O2 in the gas phase. The technique has been used to assay cell survival in tumours treated in vivo with cytotoxic agents, and examples are given of survival curves obtained from a pancreatic tumours irradiated with gamma-rays and a colonic tumour from mice treated with cyclophosphamide. The results obtained by this in vitro method are in agreement with those from the agar diffusion chamber technique. This culture method has also been successfully used for the growth of cells taken directly from human tumour biopsy samples obtained in the clinic.

Animals↗
PubMed1978

In vitro radiation response of cells from four human tumors propagated in immune-suppressed mice.

Two recently developed clonogenic assays for human tumor cells have been used to measure the in vitro radiation cell survival of four human tumors, a pancreatic carcinoma, a colonic carcinoma, an oat cell carcinoma of the lung, and a melanoma, propagated as xenografts in immune-suppressed mice. The slopes and shoulders of the survival curves for the first three tumors were all similar with Do's, respectively, of 94, 100, and 131 rads and with Dq's, respectively, of 8, 44, and 41 rads, However, melanoma cells from the fourth tumor had a survival curve that differed from those of the other three, both in having a wider shoulder with a Dq of 216 rads and in having a shallower slope with a Do value of 183 rads. It is suggested that the wide shoulder to the melanoma cell survival curve may in part explain the poor response to small fractionated doses of radiotherapy usually observed clinically for this tumor type. However, the data from the other three tumors suggest that differences in radiotherapeutic response seen in the clinic for these tumors cannot be attributed to differences in intrinsic radiosensitivity of the tumor cells.

Animals↗
PubMed1979

[Cholestasis after renal transplantation and immune-suppressive therapy (author's transl)].

A 39 year old female patient developed jaundice 16 months after having received a renal transplant. Intrahepatic cholestasis was diagnosed on the basis of serum enzyme concentration patterns and of histology of a liver biopsy specimen; it was thought to be due to immune-suppressive therapy. Azathioprine was stopped and the hepatic situation normalized within 5 months. HBs-infection was present at the same time, so it is being discussed, if this condition may have influenced the development of intrahepatic cholestasis as well. It has to concluded from this case report, that liver function of patients with renal transplants receiving azathioprine has to be controlled regularly. Stopping azathioprine may induce normalization of even severely damaged liver function without influencing the function of the renal transplant.

Adult↗
PubMed1979

Immune suppression of erythropoiesis in transient erythroblastopenia of childhood.

Serum and IgG from four children with transient erythroblastopenia of childhood (TEC) was tested to see what effect it would have on development of erythroid colonies from bone marrow mononuclear cells. Serum and IgG specimens obtained at the time of diagnosis uniformly suppressed erythroid colony development from CFU-E. Washed bone marrow mononuclear cells from a child with TEC failed to grow in the presence of his own serum, but grew normally in the presence of isologous serum. Serum specimens obtained from patients after recovery from TEC had no effect on erythroid colony development. The anemia of TEC appears to be due to transient immune suppression of erythroid colony development.

Anemia, Aplastic↗