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At least 19 recordsLinked to original sources
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. I. Tentative hypothesis for the induction of antigen-specific suppression by antigen-immunosuppressive-agent conjugates].

The most important mechanisms for the specific depression of immune reactions--immuno-tolerance, enhancement, transfer of antibodies, drug induced tolerance, immunological suicide, application of antibody-toxin-complexes--are discussed with regard to their possible application in the clinical practice. A tentative hypothesis for induction of antigen specific suppression is proposed, basing on the use of antigen-immunosuppressive agent-conjugates (AIC). Antigen binding lymphocytes are supposed to bind the AIC and to pick them up through endocytosis. After breakdown of the AIC in the lymphoid cells the free immunosuppressive agent can become effective causing damage to the specific cell clones.

Animals↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. II. Immunogenicity of antigen-immunosuppressive-agent conjugates].

The maintenance of specific immunogenicity of carrier proteins is a necessary condition for the successful use of antigen-immunosuppressive agent-conjugates (AIC) for an antigen specific suppression of the immune response. The experimental results indicate that, in spite of the binding of 6-mercaptopurine (6-MP) and toluyl (T) to bovine gamma globulin (BGG) and human serum albumin (HSA), the carrier specific immunogenicity is not significantly altered. The intradermal application of 6-MP-BGG and T-BGG emulsified with complete Freund's adjuvant in guinea pigs results, in all cases, in a well detectable anti BGG hemagglutination and precipitation titer. This kind of immunization leads also to a formation of anti 6-mercaptopurine and anti new antigen determinants (NAD's) antibodies.

Animals↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. IV. Studies on the specific suppression of humoral immune response in guinea pigs by antigen-immunosuppressive-agent conjugates].

Bovine gamma globulin (BGG) antigens were modified by the binding of 6-mercaptopurine and toluyl residues, and their influence on the humoral immune response in guinea pigs was investigated. The antigen-immunosuppressive agent-conjugates (AIC) were different, depending on the method used for their preparation and the number of coupled residues per one molecule of BGG. Conjugates denoted as MPI-n-BGG were prepared by special chemical binding of corresponding thioisocyanates. MPII-n-BGG were synthetized by acetylation, and MPIII-n-BGG conjugates, by reductive alkylation. Pretreatment of guinea pigs with MPIII-19-BGG, MPII-16-BGG resulted in a stimulatory effect on the subsequent humoral immune response induced by BGG application. A significant suppressive influence was detectable if the animals had been pretreated with MPII-6-BGG and MPI-26-BGG. MPI-13-BGG and MPI-36-BGG had no effect on the later induced anti-BGG antibody formation. The immune response against a second antigen (human serum albumin) was not influenced by this kind of pretreatment of the animals. Therefore it seems justified to conclude that both stimulatory and suppressive effects seen here were antigen specific and that both the method for chemical modification and the number of coupled 6-MP residues are very important for their effectivity.

Agglutination↗
PubMed1976

Immunosuppression by Moloney leukemia virus: lack of correlation between virus replication and the immunosuppressive effect.

Young adult mice were infected with 10(4) plaque-forming units (PFU) or Moloney murine leukemia virus M-MuLV. Two different virus preparations were used: a) M-MuLV obtained from serial passage in mice [animal passage (AP)] and b) tissue culture (TC)-grown virus harvested after three in vitro passages of the AP M-MuLV in fibroblasts. Replication of TC and AP M-MuLV in spleen cells was determined by an infectious center (IC) assay at 1 and 2 weeks after the infection. Immune responsiveness of spleen cells was evaluated in challenge with sheep red blood cells (SRBC) and subsequent enumeration of antibody plaque-forming cells (PFC). TC M-MuLV replicated faster in the spleen than did AP M-MuLV and reached about 10- to 100-fold higher titers. However, the response of anti-SRBC PFC, suppressed to the same degree in the spleens of mice infected with TC or AP virus, was from 10 to 50% of the control response. A comparison of virus replication with the anti-SRBC response in aliquots from the same spleens showed no correlation between virus IC and antibody PFC. Both TC and AP M-MuLV induced the expression of virus-specific, cell membrane antigen on spleen cells. These findings indicated a divergence between virus replication on the one hand and the immunosuppressive effect and the cell membrane alteration on the other.

Animals↗
PubMed2026

Electronic Nudges to Increase Influenza Vaccination in Immunosuppressed Adults Across the Age Spectrum: A Pooled Analysis of 2 Nationwide Randomized Trials.

BACKGROUND: Immunosuppressed individuals face higher risk of severe influenza complications, yet vaccination coverage remains low. We aimed to assess the effect of electronic letter-based nudges on influenza vaccination uptake by immunosuppression status. METHODS: We performed a participant-level pooled analysis of 2 methodologically harmonized, nationwide, pragmatic randomized clinical trials during the 2023-2024 influenza season. Adults aged &#x2265;65 years (NUDGE-FLU-2) and adults aged 18-64 years with chronic conditions (NUDGE-FLU-CHRONIC) were included, with immunosuppression defined by an immunosuppressive diagnosis or a filled prescription for immunosuppressive therapy. Participants were randomized in a 2.45:1:1:1:1:1:1 ratio to usual care or 1 of 6 electronic letter interventions. The primary outcome was receipt of influenza vaccination by 1 January 2024 ascertained from nationwide administrative health registries. Effect modification by immunosuppression status was assessed using binomial regression. RESULTS: Among 1 181 254 participants (mean age 67 years; 73 830 [6.3%] immunosuppressed), 66.1% were vaccinated. Any letter increased vaccine uptake compared with usual care (absolute difference, 2.79% points; 95% confidence interval [CI], 2.60-2.98; P < .001), with greater effect among immunosuppressed individuals (+4.12 vs +2.70% points; Pinteraction = .002). In younger adults with chronic conditions, letter-based nudges increased vaccination rates by 11.7% points overall and by 13.3% points among those with immunosuppression (Pinteraction = .007). Among immunosuppressed individuals, nudging effects appeared greater for those with immunosuppressive conditions than for those receiving immunosuppressive treatment. CONCLUSIONS: Electronic letter-based nudges increased influenza vaccination rates, with greater benefit among immunosuppressed individuals. These findings support implementation of low-cost, letter-based nudging strategies to improve vaccine uptake in this high-risk population. Clinical Trials Registration. NCT06030726 and NCT06030739.

Adolescent↗
PubMed1979

Correlation between anergy and a circulating immunosuppressive factor following major surgical trauma.

In order to clarify the relationship between anergy and immunosuppressive activity in the serum, we studied 46 previously well patients before and at three, five, seven and 28 days after surgery. Delayed hypersensitivity was measured by skin testing with four common recall antigens, and serum immunosuppressive activity was determined by the ability of the patient's serum in 10% concentration to suppress by 50% or more the phytohemagglutinin (PHA) stimulation of normal human lymphocytes as compared to pooled normal serum. Prior to surgery, all patients manifested delayed hypersensitivity to one or more antigens, and no patient had immunosuppressive serum. Fifteen patients underwent minor surgery under general anesthesia and did not develop anergy or immunosuppressive serum. Thirty-one patients underwent major cardiovascular surgery. Thirteen of these patients became anergic by day 3 after operation, and 11 of the 13 developed immunosuppressive serum. Eighteen patients maintained delayed hypersensitivity after major surgery, and only three developed immunosuppressive serum. The correlation between anergy and immunosuppressive serum was highly significant (p < 0.001). There was a significant difference in the degree of suppressive activity in the serum of the anergic and reactive patient groups for each postoperative day studied until day 28, when there was recovery of delayed hypersensitivity and lack of immunosuppressive serum. The occurrence of postoperative anergy and immunosuppressive serum was not related to the patient's age, sex, number of perioperative blood transfusions or duration of anesthesia but was associated with an increase in postoperative infectious complications (p < 0.05) and in postoperative days in the hospital (p < 0.01). Pooled immunosuppressive serum from anergic patients was fractionated by ion exchange chromatography, gel filtration and preparative high voltage electrophoresis. The majority of the immunosuppressive activity could be accounted for by an electrophoretically homogenous polypeptide-containing fraction not identified in the serum of patients undergoing minor surgery or in normal individuals. We conclude that anergy occurring after major operative trauma is associated with the appearance of a circulating immunosuppressive molecular species and that these events are in turn associated with increased patient morbidity and increased length of hospitalization.

Adult↗
PubMed1978

Effect of immunosuppression on the growth of six murine tumors.

Mice have been immunosuppressed with cyclophosphamide, cortisone-acetate, irradiation, or Ehrlich ascitic fluid (EAF) and then grafted with Ehrlich tumor or with one of the following strain-specific tumors: thymoma, methylcholanthrene-induced fibrosarcoma, B-16 melanoma, lymphatic leukaemia, and myeloid leukaemia. Immunosuppression of the host influenced very differently the growth of transplanted malignancies. The growth of thymoma and of Ehrlich tumor was regularly enhanced. The growth of fibrosarcoma and of melanoma, on the other hand, was retarded in mice pretreated with EAF and X-rays, or remained unchanged in mice pretreated with drugs. Leukaemia growth was not influenced by any immunosuppressive treatment; the only exception was enhanced growth of lymphoid leukaemia in animals pretreated with EAF. Thus different tumors grew differently in animals immunosuppressed by the same immunosuppressive agent, while different immunosuppressive treatment changed the growth of one particular tumor always in the same way. From this we concluded: (1) there is no rule as to how immunosuppression of the host will influence tumor growth; and (2) the way in which the malignant growth will be changed depends mainly upon the type of the tumor and probably not very much upon the type of immunosuppressive treatment.

Animals↗
PubMedDate not supplied

Coccidioidomycosis in potentially compromised hosts: the effect of immunosuppressive therapy in dissemination.

Charts of 126 patients with coccidioidomycosis were reviewed. Sixteen of these were patients who had malignancies, uremia, or a collagen-vascular disease and/or had received recent immunosuppressive drug therapy. The rate of disseminated infection was 50% in this group. (The dissemination rate was 14% in 110 control patients.) No case of dissemination occurred in patients who only had the above underlying diseases; all cases of dissemination were among those who had received immunosuppressive therapy. The dissemination rate in control patients was higher for patients age 40 or over than for younger patients. The dissemination rate showed no age-related difference, however, in patients treated with immunosuppressive drugs. The dissemination rate was similar in control patients of both sexes and uniformly higher for both immunosuppressively treated males and females. The dissemination rate did not appear to be influenced by the number of circulating lymphocytes if the patient had received immunosuppressive drugs. Patients with disseminated disease who had received immunosuppressive drugs were capable of producing a serological response to the coccidoiidal organism in high titer but none had positive skin test reactivity. Disseminated coccidioidomycosis is not uniformly fatal in the immunosuppressed host: half of our patients are alive an average of 33 months after diagnosis.

Adolescent↗
PubMed2025

Immunosuppressants Rewire the Gut Microbiome-Alloimmune Axis Through Time-Dependent and Tissue-Specific Mechanisms.

BACKGROUND: Lifelong immunosuppressive therapy is required to prevent allograft rejection in organ transplantation. Current immunosuppressants effectively suppress adaptive and innate immune responses, but their broad, antigen-non-specific effects often result in severe off-target complications. It remains a significant unmet medical need in transplant medicine. RESULTS: In this study we investigated immunosuppressant effects of four major immunosuppressant classes, including tacrolimus, prednisone, mycophenolate mofetil (MMF), and fingolimod (FTY), on the gut microbiome, metabolic pathways, lymphoid architecture and lymphocyte trafficking after up to 30-day chronic exposure. Despite their distinct mechanisms of action and not designed to target the gut, all immunosuppressive drugs induced profound and time-dependent alterations in both intestine gene expression and gut microbiome composition. Progressive alterations from moderate early, drug-specific changes to a strikingly convergent microbial dysbiosis, marked by significant expansion of pathobionts of Muribaculaceae, occurred across all drug classes. Concurrently, all drugs uniformly induced significant suppression of mucosal immunity including B cell, immunoglobulin, and antigen recognition. Time-dependent changes in lymph node (LN) reorganization and cellular composition were also observed, marked by a progressive shift toward pro-inflammatory phenotypes in gut-draining mesenteric LNs and a gradual loss of tolerogenic architecture in peripheral LNs. Drug-specific metabolic alterations and distinct phases of intestinal transcriptional responses were also characterized. Notably, MMF and FTY demonstrated the most robust immunomodulatory properties, and were able to suppress alloantigen-induced inflammation through mediating regulatory T cell distribution and LN remodeling. CONCLUSIONS: Together, these findings highlight the underappreciated complexity and temporal dynamics immunosuppressants effects, particularly their impact on the gut and compartmentalized regulation of alloimmune in lymphoid tissues. Understanding these relationships offers new opportunities for refining immunosuppressive strategies to reduce treatment-related off-target complications and improve long-term organ transplant outcomes.

gut dysbiosis↗
PubMed1975

[Immunosuppressive therapy in renal disease (author's transl)].

Since immunological events were found to be pathogenetically involved in various forms of glomerulonephritis, corticosteroids and immunosuppressive drugs were introduced in the treatment of nephritis. However, as opposed to the findings in the paediatric nephrotic syndrome, controlled and multicentric trials with immunosuppressive therapy revealed disappointing results in the management of renal disease in adults. Significantly better results under immunosuppressive therapy, were seen only in the nephrotic syndrome based on the so-called "no changes" or "minimal changes" nephritis. In chronic membranous and proliferative glomerulonephritis the clinical course in the treated group was not statistically different from that of the untreated group. In some disorders of connective tissues, such as systemic lupus erythematosus, polyarteritis nodosa and Wegener's granulomatosis, corticosteroids and immunosuppressive agents seem to exert a favourable effect on the course of renal disease. Encouraging results concerning the combined use of immunosuppressive drugs, anticoagulants and platelet aggregation inhibitors in mesangiocapillary (membrano-proliferative) glomerulonephritis and rapidly progressive nephritis have also been presented. Several factors such as incomplete immunosuppression, druginduced antigen tolerance and increased immune complex formation as a consequence of inhibited antibody production may contribute to the fact that many patients with different forms of nephritis do not benefit from long-term immunosuppressive therapy.

Adult↗
PubMed2026

Spatial biology reveals altered macrophage states in immunosuppressed non-melanoma skin cancer.

Immunosuppressed patients with non-melanoma skin cancer experience worse clinical outcomes, yet the tumor immune microenvironment associated with systemic immunosuppression remains incompletely defined. Using integrated single-cell, spatial transcriptomic, multiplex immunofluorescence, and spatial epigenomic profiling across immunocompetent and immunosuppressed tumors, we found that overall immune-cell composition was largely preserved despite differences in immune-cell distribution, spatial organization, and T cell clonality. Immunosuppressed tumors demonstrated reduced intratumoral macrophage densities, decreased T cell clonal diversity, altered antigen-presenting cell and T cell spatial interactions, and distinct fibroblast- and macrophage-associated spatial niches. Multi-cohort validation across complementary spatial and single-cell platforms identified consistent alterations in innate-adaptive immune organization in immunosuppressed tumors. Together, these findings define spatial and functional remodeling of the tumor immune microenvironment under systemic immunosuppression and provide a framework for future therapeutic investigation in high-risk patients.

Humans↗
PubMed1976

Cytomegalovirus infection in patients receiving immunosuppressive therapy for rheumatologic disorders.

Evidence of cytomegalovirus infection was sought in 131 patients attending a rheumatology clinic, 211 blood donors, and 14 patients before and after the initiation of cytotoxic immunosuppressive therapy for a rheumatologic condition. The titer of complement-fixing antibody to cytomegalovirus was significantly related to age and sex, but not to rheumatologic disease. After adjustment for age and sex differences, the proportion of patients treated with corticosteroids who had measurable antibody was lower than that of controls (P less than 0.025). Immunosuppressive therapy with azathioprine or cyclophosphamide did not affect the proportion of patients with antibody, but there was a significantly increased titer of antibody in those who were seropositive (P = 0.04). Cytomegalovirus was isolated from the urine of 20% of patients receiving cytotoxic immunosuppressive drugs, but not from any of the patients receiving corticosteroids or neither form of therapy (P = 0.001). Eight of 14 patients followed prospectively after the initiation of therapy with immunosuppressive drugs became infected with cytomegalovirus as demonstrated by a fourfold or greater rise in complement-fixing titer, viruria, or both. Seven of the eight patients were seropositive before therapy, a finding suggesting that immunosuppression acts largely by reactivating latent infection. It is postulated that immunosuppressive agents alone may account for a large proportion of cytomegalovirus infections seen after allograft transplantation.

Adrenal Cortex Hormones↗
PubMed1976

Cessation of immunosuppression after renal transplantation.

Five recipients of successful living related donor kidney transplants stopped azathioprine and prednisone against medical advice. Two recipients who were nonidentical by human leukocyte (HL-A) serotyping and mixed leukocyte culture (MLC) became uremic again after cessation if immunosuppression for periods of 2 and 6 months. Both patients died while refusing to reinstitute iunosuppression and their kidneys showed severe rejection histologically. Three recipients of MCL and HL-A identical kidneys were off azathioprine and prednisone for periods of 7, 12, and 30 months, respectively. None developed changes in renal function. Two patients currently are back on immunosuppression. The third recipient remains stable although off immunosuppression for 36 months; her cessation of immunosuppression was elicited by a mailed questionnaire sent to all recipients following detection of the first four. In addition to these five patients, three recipients of cadaver kidneys lost graft function after lapses in immunosuppression. This represents a 4% incidence of major lapses in immunosuppression (excluding known cessation during sepsis). The clinical outcome depended on degree of histocompatibility as best measured by MLC.

Adolescent↗
PubMed1978

[Immunosuppression as a concomitant effect].

1. It is becoming increasingly clear that besides traditional immunosuppressive agents, an array of miscellaneous influences and conditions, as well as drugs used for other purposes, can affect the immune system. The potential pathogenetic role of immunity in an ever growing number of diseases, including infections, cancer, and autoimmune processes, confers on the concept of concomitant immunosuppression or immunotoxicology its due place in the discipline of immunopharmacology. 2. Microorganisms such as viruses, bacteria, and protozoa (and their products), as well as parasites, may depress immune reactivity. The mechanism of action, dose-response dependency, effect of timing, and relation to bacterial adjuvanticity need more thorough exploration. 3. The efficacy of immunosuppressive drug protocols can be improved by combining immunosuppressants without bone marrow toxicity, such as niridazole or free fatty acids, with the standard antiproliferative immunosuppressive agents. 4. Prostaglandin is a likely candidate for an essential role as an immunosuppressive effector. Its release from T-suppressor cells is triggered for example by microorganisms. Moreover, dietetic and metabolic factors, such as free fatty acids, and nervous impulses affect prostaglandin formation. If thus constitutes a link between the nervous system and, on the other hand, immunity and possibly cancer.

Adjuvants, Immunologic↗
PubMed1979

Immunosuppressive antilymphocyte serum. III. Different subpopulations of T lymphocytes are influenced at different doses of antilymphocyte serum.

In these experiments, we have examined the effect of antilymphocyte serum (ALS) on T lymphocyte subpopulations in animals receiving nonimmunosuppressive, weakly immunosuppressive, and strongly immunosuppressive doses of different pools of ALS. Nonimmunosuppressive (inactive) sera were defined by their inability to prolong Fischer skin grafts on Lewis recipients. Weak immunosuppression was considered to have been achieved at doses of active ALS that induced prolonged survival of Fischer skin homografts but not the more strongly antigenic Wistar-Furth homografts. Similarly, strong immunosuppression was induced with doses of active ALS that resulted in prolonged survival of not only Fischer but also the Wistar-Furth grafts. Examination of Lewis rats treated under these conditions indicated that weakly immunosuppressive ALS created a shift in peripheral T lymphocyte subpopulations with an increase in the absolute numbers of one subpopulation (lymphocytes capable of forming rosettes with guinea pig red blood cells in fetal calf serum). This population shift induced by active ALS was dose dependent and occurred in spleen slightly before lymph nodes. Nonimmunosuppressive antisera failed to induce this change. Moreover, although these doses of ALS were capable of prolonging the survival of Fischer skin grafts and inducing the population change, there was no loss of reactivity to phytohemagglutinin (PHA) and concanavalin A (Con A) in vitro. However, at doses of antiserum capable of prolonging the survival of Wistar-Furth skin grafts, the in vitro reactivity of T lymphocytes to these mitogens was more consistently suppressed. These data suggested that the degree of immunosuppression achieved with different pools or doses of ALS was attributable to variation in the susceptibility of different T lymphocyte subpopulations to suppression by ALS.

Animals↗
PubMed1979

Suppression of T cell-mediated immunity by tumor cells: immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors.

In studying the immunogenicity of spleen cells and tumor cells in the generation, of cytotoxic T lymphocyte (CTL) in the allogeneic mixed lymphocyte culture (MLC) or mixed lymphocyte tumor cell culture (MLTC) reactions, we have found that the tumor cells not only appear to be poorly immunogenic, but are also immunosuppressive. This was shown by the ability of the tumor cells or their cell-free extracts to suppress standard MLC reactions. This suppression was acting mainly at the induction phase of the cytotoxic response. It could not interfere with the killing activity of the fully generated CTLs. In a Friend virus-induced leukemia FBL-3 system, at least two major components could be attributed to the cause of immunosuppression; one was of viral origin and the other was of non-viral origin. The viral component was sensitive to UV-irradiation and could be pelleted after ultracentrifugation at 100,000 g. The non-viral component was UV-resistant and was retained in the supernatant fraction after ultracentrifugation. Friend virus and 12 commonly found murine viruses have been excluded as the possible candidates causing the immunosuppression. The immunosuppressive viruses are very likely of endogenous origin and are defective in replication as shown by electromicroscopy, and by the virus focus-inducing and reverse transcriptase assays. These findings indicate that probably all tumor cells possess the immunosuppressive factor(s) which may account for their apparent lack of immunogenicity and the lack of proper immune responses in the tumor-bearing hosts.

Animals↗