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At least 811 records · Page 45Linked to original sources
PubMed2005

EBV and systemic lupus erythematosus: a new perspective.

We have proposed that EBV uses mature B cell biology to access memory B cells as a site of persistent infection. A central feature of this model is that EBV adapts its gene expression profile to the state of the B cell it resides in and that the level of infection is stable over time. This led us to question whether changes in the behavior or regulation of mature B cells would alter the state of EBV persistence. To investigate this, we studied the impact of systemic lupus erythematosus (SLE), a disease characterized by immune dysfunction, on EBV infection. We show that patients with SLE have abnormally high frequencies of EBV-infected cells in their blood, and this is associated with the occurrence of SLE disease flares. Although patients with SLE have frequencies of infected cells comparable to those seen in immunosuppressed patients, in SLE the effect was independent of immunosuppressive therapy. Aberrant expression of viral lytic (BZLF1) and latency (latency membrane proteins 1 and 2a) genes was also detected in the blood of SLE patients. We conclude that the abnormal regulation of EBV infection in SLE patients reflects the sensitivity of the virus to perturbation of the immune system.

Adult↗
PubMedDate not supplied

Immunobiology of left ventricular assist devices.

The increasing use of implanted biomaterial devices has made it evident that no material is biologically inert. As a result of direct contact with elements of the blood circulation, such as during hemodialysis or after left ventricular assist device (LVAD) implantation, significant changes in systemic immunologic and thrombostatic functions occur. The clinical success of LVAD implantation has, nevertheless, been accompanied by complications arising from an aberrant state of monocyte and T-cell activation, leading to heightened susceptibility of circulating CD4 T cells to undergo activation-induced cell death; this results in progressive defects in cellular immunity and an increased risk of serious infection. Because of the increased state of T-cell activation and the selective loss of Th1 cytokine producing CD4 T cells, LVAD recipients also develop B-cell hyperreactivity and dysregulated immunoglobulin syntheses by unopposed production of Th2 cytokines and increased CD40 Ligand-CD40 interactions. LVADs are currently being evaluated as a permanent therapy for end-stage heart failure. Because these immune dysfunctions appear to be related to the effects of excessive biomaterial associated T-cell activation, future efforts will need to be directed at either altering the physical properties of the materials interacting with the host circulation or pharmacological intervention aimed at inhibiting T-cell activation.

Autoimmunity↗
PubMed1990

[Suppression of lymphocyte function 2 years following surgical treatment of paranasal sinus mycosis].

Prior investigations showed that acutely diseased patients with an aspergillus sinusitis manifested immune dysfunctions in respect of both T and B lymphocytes. In contrast to patients with nonmycotic sinusitis reduced in vitro and in vivo responsiveness was observed. The aim of this study, carried out after removal of the fungus ball and endoscopic surgery in clinically healthy patients, was to ascertain whether this reduced responsiveness was to be regarded as the effect or cause of an Aspergillus fumigatus infection. Two years later, the in vivo response to recall antigens was normal in both groups of patients, whereas the response to mitogens (ConA, PHA and PWM) was still decreased in the aspergillus sinusitis groups. The data suggest that the reduced immune response is a consequence of the Aspergillus fumigatus infection. Depressed skin reactivity is only present during acute infection, while proliferative capacity, as measured in the "whole blood stimulation" assay is depressed for a long time after healing the acute infection.

Adult↗
PubMed1997

Rheumatoid arthritis: autoreactive T cells recognising a novel 68k autoantigen.

OBJECTIVE: A 68k autoantigen has been identified by specific antibodies from patients with rheumatoid arthritis (RA). This study considered whether or not this antigen is a target for T cells and thus may play a part in T cell mediated immunopathology of active RA. METHODS: The 68k antigen was isolated and used in a nitrocellulose bound form to stimulate T cells. Proliferation of T lymphocytes of peripheral blood as well as synovial fluid was measured. RESULTS: Peripheral blood T cells specifically proliferating against the 68k antigen were detected in 19 of 27 patients with RA (70%). For T cells isolated from peripheral blood, proliferation peaked on day 10. When T cells were isolated from actively inflamed synovial fluid, the proliferation kinetics shifted to a peak on day 3. Blockade of HLA class II antigens resulted in an increase of proliferation in the case of HLA-DP. Applying HLA-DP specific antibodies capable of inhibiting antigen presentation mediated by this molecule, T cells of 17 of 27 RA patients (63%) proliferated to a higher extent than with the 68k antigen alone. The phenomenon that an increased proliferation occurred upon blockade of a particular HLA class II family member was also demonstrated for DQ and DR: the 68k antigen likewise stimulated T cells restricted for DP or DQ, respectively. CONCLUSIONS: The novel 68k antigen is a target of both T and B cellular immune responses and as such could play a part in the immune dysfunction of RA. The finding that blocking of certain HLA class II molecules functioning in antigen presentation (for example, via HLA-DQ) results in a higher instead of lower proliferation in vitro, may argue for the presence of antigen specific suppressive T cells.

Adult↗
PubMed1989

Encephalopathy as a presentation of pediatric AIDS: case report.

Fifty to ninety percent of pediatric AIDS cases are complicated by neurologic dysfunction. We present a case of a 5-year-old black female with AIDS encephalopathy and Mycobacterium avium intracellulare. Her initial presentation was that of neuroencephalopathy with loss of developmental milestones, pyramidal tract signs, and subsequent evidence of cortical atrophy. Her initial CT scan at the time of frank encephalopathy was normal, whereas 18 months into the clinical course of her encephalopathy, her CT scan of the head demonstrated typical ventricular dilatation and severe cortical atrophy consonant with her clinical picture. She subsequently developed Mycobacterium avium intracellulare documented by gastric aspirate culture and other opportunistic infections including Candida esophagitis. Her neuroencephalopathy plateaued with continued evidence of immune dysfunction and mycobacterium by gastric aspirate, despite triple antibiotic therapy with INH, streptomycin, Pyrazinamide with later addition of Rifampin and final substitution of the investigational congener Rifabutin. AIDS encephalopathy and Mycobacterium intracellulare are discussed in terms of their prognosis and therapy, particularly in view of new reports of the application of AZT and immunoglobulin therapy.

AIDS Dementia Complex↗
PubMed1993

Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants.

In asymptomatic human immunodeficiency virus (HIV) infection in humans, disturbed T cell functions such as anergy and programmed cell death, thought to result from inappropriate signaling by antigen-presenting cells due to HIV infection, precede increase in virus load, decline in CD4+ T cell numbers, and subsequent disease progression. Here, in 3 long-term HIV-1-infected asymptomatic chimpanzees, antigen-presenting cell function was intact and T cells had normal proliferative capacity with no evidence of HIV-1-associated programmed cell death. Polymerase chain reaction analysis demonstrated low frequencies of cells harboring proviral DNA. Primary virus isolation from the infected animals demonstrated the absence of monocytotropic HIV-1 variants, in concordance with complete insusceptibility of chimpanzee monocytes for HIV-1 infection. Possibly, because of the incapacity of HIV-1 to infect monocytes, systemic immune dysfunction will not occur, contributing to controlled viral replication and maintenance of the asymptomatic state in HIV-infected chimpanzees.

Amino Acid Sequence↗
PubMed2004

Sex steroid-mediated regulation of macrophage/monocyte function in a two-hit model of trauma-hemorrhage and sepsis.

Studies have shown that 17beta-estradiol has salutary effects on immune functions after trauma-hemorrhage (TH). It remains unknown, however, whether 17beta-estradiol has a similar effect in a double-hit model of TH and subsequent sepsis. It is also unknown if under those conditions the circulating immune cells accurately represent immunological responses occurring in fixed tissues, such as the spleen. To study this, pre-castrated mice were hormonally treated and then subjected to soft-tissue trauma (i.e. midline laporatomy), hemorrhagic shock (MAP 35+/-5mmHg for 90 min followed by resuscitation) and 24 h later sepsis was induced by cecal ligation and puncture (CLP). Splenic macrophages (SMphi) and peripheral blood mononuclear cells (PBMC) were isolated and cultured with LPS. 5alpha-Dihydrotestosterone-treated mice showed a depressed pro-inflammatory cytokine production after TH-sepsis in both SMphi and PBMC. In contrast, the 17beta-estradiol treated groups showed suppressed pro-inflammatory cytokine production in the PBMC population under those conditions. In summary, 17beta-estradiol was able to prevent immune dysfunction after TH and subsequent sepsis. However, the beneficial effects of 17beta-estradiol were limited to tissue-fixed Mphi, suggesting compartmentalization of the response. Thus, events occurring in the tissue-fixed cells are not necessarily reflected in the circulating PBMC population.

Animals↗
PubMed2000

Modulatory role of the epinergic system in the neuroendocrine-immune system function.

It is well recognized that the reciprocal interaction established between the immune and neuroendocrine systems is crucial for the homeostatic adaptation of individuals during septicemia. In the present study, using an in vivo rat model, we investigated the degree of participation of central and peripheral epinergic systems in the modulation of the hypothalamic-pituitary-adrenal and immune axes' functions during endotoxemia. For this purpose, acute endotoxemia was induced in adult male rats pretreated intraperitoneally with either different inhibitors of phenylethanolamine-N-methyltransferase (PNMT) [which are active either peripherally (SKF 29661) or both peripherally and centrally (SKF 64139), thus lowering epinephrine (EPI) synthesis] or vehicle only (CTRL). Twelve hours after pretreatment, animals were intraperitoneally injected with vehicle alone (basal) or vehicle containing bacterial lipopolysaccharide (LPS) and sacrificed 2 h later. A significant (p < 0.05 vs. the respective basal value) hypoglycemia was found in all groups studied. No pretreatment modified basal plasma adrenocorticotropic hormone (ACTH), glucocorticoid and cytokine concentrations. Endotoxin-stimulated ACTH secretion was severalfold (p < 0.05) higher than the respective basal value in CTRL and in SKFs-pretreated rats; however, the plasma ACTH levels after LPS were significantly (p < 0.05 vs. CTRL and SKF-29661 values) reduced in SKF-64139-pretreated rats. All groups studied showed an appropriate adrenal response to endotoxin challenge. Although no differences were found in basal anterior pituitary (AP) ACTH content among groups, LPS treatment significantly (p < 0.05 versus the respective basal value) decreased AP ACTH in CTRL and SKF 29661 groups. No pretreatment modified the basal medial basal hypothalamus (MBH) corticotropin-releasing hormone (CRH) content. Conversely, SKF 64139 pretreatment significantly (p < 0.05 vs. CTRL and SKF 29661 values) reduced basal median eminence (ME) CRH content, and LPS administration significantly (p < 0.05) decreased ME CRH in CTRL and SKF-29661-pretreated rats. SKF 64139 pretreatment significantly (p < 0.05) enhanced basal MBH and ME arginine vasopressin (AVP) contents. LPS administration significantly (p < 0.05) decreased MBH AVP in CTRL and SKF-29661-pretreated rats and diminished (p < 0.05 vs. basal values) ME AVP in all groups. The plasma tumor necrosis factor alpha (TNFalpha) concentrations were enhanced severalfold (p < 0.05 vs. basal values) after LPS treatment in CTRL rats, but not in SKFs-treated animals. In order to explore the reduced cytokine release after LPS in PNMT-inhibited rats, additional ex vivo experiments were performed by using peripheral mononuclear cells (PMNC) from both CTRL and SKF-29661-pretreated rats. The results of these experiments confirmed an immune dysfunction after inhibition of peripheral EPI synthesis; in fact, basal and concanavalin-A-stimulated TNFalpha secretions were significantly (p < 0.05) lower in SKF-29661-treated than in CTRL PMNC, while, interestingly, addition of EPI (10(-7) M) to the medium fully restored these effects. These data demonstrate that: (1) the mechanism whereby LPS-induced hypoglycemia was independent of epinergic activity; (2) selective central inhibition of epinergic function reduced endotoxin-stimulated ACTH secretion, an effect that could mainly be due to a decrease in CRH-ergic activity; (3) the central epinergic system positively and negatively modulates CRH- and AVPergic functions, respectively, and (4) inhibition of peripheral PNMT activity reduced immune system function in vivo and ex vivo. It is further suggested that low peripheral levels of EPI could be beneficial for the body's defense mechanisms during endotoxic shock.

Acute-Phase Reaction↗
PubMedDate not supplied

Interleukin-7 (IL-7): immune function, involvement in the pathogenesis of HIV infection and therapeutic potential.

Interleukin 7 (IL-7), which is constitutively produced particularly by stromal cells from the bone marrow and thymus, plays a crucial role in T cell homeostasis. This cytokine is implicated in thymopoiesis since it sustains thymocyte proliferation and survival. It regulates peripheral naive T cell survival by modulating the expression of the anti-apoptotic molecule Bcl-2, and sustains peripheral T cell expansion in response to antigenic stimulation. Infection by the human immunodeficiency virus (HIV) leads to severe T lymphopenia and general immune dysfunction. Increased IL-7 plasma levels are generally observed in HIV-infected patients. The existence of an inverse correlation between IL-7 plasma levels and the CD4+ T cell count suggests that a direct feedback mechanism is working to restore peripheral T cell counts in lymphopenic patients. Here, IL-7 plasma levels are a good predictive marker of CD4+ T cell restoration during therapy. Combinations of antiretroviral treatments considerably slow disease progression. They drastically decrease the viral load and, in most patients, significantly increase peripheral CD4+ T cell counts. However, despite their usual ability to reduce viral replication, such treatments often fail to reverse lymphopenia and do not restore specific antiviral immune responses. IL-7, based therapy, combined with efficient antiretroviral treatment, may be beneficial to HIV-infected patients by promoting thymic output, sustaining naive T cell counts and increasing memory T cell activation.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Nutritional support and the surgical patient.

PURPOSE: Data on the impact of nutritional support (NS) on outcomes in surgical patients are reviewed. SUMMARY: While most patients will progress to oral nutrition after surgery and require little or no intervention, major surgery or postoperative complications can delay the prescription of an oral diet. In such patients, nutritional requirements are often increased to support wound healing and hypermetabolism associated with surgical recovery. Without adequate nutrition, muscle wasting, immune dysfunction, and declining visceral protein status are observed. While it would seem intuitive that early nutritional intervention is warranted for most patients, the literature to date suggests that early parenteral nutrition (PN) does not improve clinical outcomes. An exception may be for severely malnourished patients if NS is provided for at least seven days preoperatively. Such patients should be identified early through nutritional assessment. Early enteral nutrition (EN) may potentially improve patient outcomes compared with PN, but there are insufficient data to confirm this. High-dose parenteral glutamine may reduce infectious complications and the length of hospitalization for surgical patients, but a significant reduction in mortality has not been observed. Early EN with immune-enhancing formulas appears promising for general surgery patients. However, their use in the critically ill surgical patient is not unanimously supported, and some studies suggest potential harm. CONCLUSION: Surprisingly little evidence is available to support a significant impact of early NS on postoperative clinical outcomes.

Education, Continuing↗
PubMed2026

SHMT2: a Metabolic and Immune Biomarker of Aggressive Lung Adenocarcinoma.

Serine/glycine-one-carbon (SGOC) metabolism is frequently altered in lung adenocarcinoma (LUAD), but its relationship to tumor behavior and predicted immunotherapy responsiveness remains incompletely defined. Metabolomic profiling of 23 paired LUAD and adjacent normal lung tissues was performed using internal extractive electrospray ionization mass spectrometry. Transcriptomic and clinical data from The Cancer Genome Atlas LUAD cohort (TCGA-LUAD) were analyzed to assess SHMT2 expression, prognosis, differentially expressed genes, and immune-related features. Predicted response to immune checkpoint blockade was evaluated using Tumor Immune Dysfunction and Exclusion (TIDE) and The Cancer Immunome Atlas (TCIA), and drug sensitivity was inferred using oncoPredict. Single-cell RNA-seq data were used to examine the cellular distribution of SHMT2. Experimental validation included quantitative reverse-transcription PCR (RT-qPCR), western blotting, Human Protein Atlas (HPA) immunohistochemistry, and short hairpin RNA (shRNA)-mediated SHMT2 knockdown followed by proliferation, wound-healing and colony formation assays. Metabolomic analysis identified glycine, serine, and threonine metabolism as a prominently altered pathway in LUAD. SHMT2 was upregulated in LUAD and associated with worse overall survival and adverse clinicopathological features. SHMT2-high tumors displayed enrichment of cell-cycle and SGOC-related transcriptional programs, lower immune and stromal scores, and reduced predicted responsiveness to immunotherapy. Single-cell analysis showed relative enrichment of SHMT2 expression in B cell populations. In vitro, SHMT2 was overexpressed in LUAD cells, and its knockdown suppressed proliferation, migration, and clonogenic growth. Collectively, SHMT2 is associated with SGOC metabolic reprogramming, aggressive tumor phenotypes, and an immune-disadvantaged state in LUAD, supporting its potential relevance as a biomarker; therapeutic targeting requires additional pharmacologic and in vivo validation.

Humans↗
PubMed2003

Local immune responsiveness following intravaginal challenge with Candida antigen in adult women at different stages of the menstrual cycle.

Recurrent vulvovaginal candidiasis (RVVC) is a significant problem in women of childbearing age and is most often caused by Candida albicans that asymptomatically colonizes mucosal tissues. Although some form of local immune dysfunction is postulated to precipitate bouts of RVVC, the normal protective vaginal host response to C. albicans is poorly understood. In an effort to stimulate the natural adaptive response to yeast in healthy women without a history of VVC, commercial Candida skin test antigen was introduced intravaginally and changes in cytokines/immunomodulators were monitored in vaginal lavage fluid pre- and post-antigen challenge. In an earlier pilot study using small numbers of women without controlling for stages of the menstrual cycle, we reported elevated cytokines in vaginal secretions of antigen challenged women. The present study, however, that employed a similar design in a large number of women during each stage of the menstrual cycle showed no evidence of local immune stimulation, including changes in Th and proinflammatory cytokines, IgE, histamine, and prostaglandin, despite a natural modulation of vaginal cytokines over the course of the menstrual cycle. Taken together, these results suggest that either some form of vaginal immunoregulation/tolerance is evident in response to yeast or that more advanced clinical designs are required to detect the normal protective vaginal response to C. albicans.

Antigens, Fungal↗
PubMed2002

Apoptosis-linked gene 2-deficient mice exhibit normal T-cell development and function.

The apoptosis-linked gene product, ALG-2, is a member of the family of intracellular Ca(2+)-binding proteins and a part of the apoptotic machinery controlled by T-cell receptor (TCR), Fas, and glucocorticoid signals. To explore the physiologic function of ALG-2 in T-cell development and function, we generated mice harboring a null mutation in the alg-2 gene. The alg-2 null mutant mice were viable and fertile and showed neither gross developmental abnormality nor immune dysfunction. Analyses of apoptotic responses of ALG-2-deficient T cells demonstrated that ALG-2 deficiency failed to block apoptosis induced by TCR, Fas, or dexamethasone signals. These findings indicate that ALG-2 is physiologically dispensable for apoptotic responses induced by the above signaling pathways and suggest that other functionally redundant proteins might exist in mammalian cells.

Animals↗
PubMed2003

Immunological anomalies and thrombocytopenia in 117 dogs and cats diagnosed with chronic fatigue syndrome (CFS).

Retrospective analysis of immune dysfunctions found in 55 dogs and 62 cats diagnosed with Chronic Fatigue Syndrome (CFS), revealed leukopenia in 11% of dogs (n = 6) and 22.5% of cats (n = 14), lymphopenia in 14.5% of dogs (n = 8) and 10% of cats (n = 6), hypogammaglobulinaemia in 9% of dogs (n = 5) and 13% of cats (n = 8) and thrombocytopenia in 20% of dogs (n = 11) and 68% of cats (n = 42). All patients had creatine kinase enzyme levels above the normal range (CK = 5-100 IU/L) and carried micrococcus-like organisms on erythrocytes. Blood cultures proved positive for Staphylococcus spp. in 16 cases. After low-dosage arsenic-based therapy (thiacetarsamide sodium) all animals experienced complete clinical remission. Subsequent controls demonstrated immune restoration in 4 representative FIV-FeLV negative cats, previously diagnosed with CFS associated with leukopenia, lymphopenia, hypogammaglobulinaemia and thrombocytopenia. The main conclusion is that a CFS-like disease in dogs and cats, characterised by the common hallmarks of high CK levels, absence of known causes of chronic fatigue in animals and presence of micrococcus-like organisms in the blood, can be associated with humoral and/or cellular immune deficiencies in 9-22.5% of cases and with thrombocytopenia in 20-68% of cases. Considerations are made on the possible role of micrococci in the aetiology of the condition and on the similarities with CFS in humans.

Agammaglobulinemia↗
PubMed2006

The role of microbes in Crohn's disease.

Despite decades of research, the etiology of Crohn's disease (CD) remains unknown. Its pathogenesis may involve a complex interplay between host genetics, immune dysfunction, and microbial or environmental factors. Microorganisms, including pathogens and members of the indigenous microbiota, may initiate or propagate the inflammatory process in CD. The pathogenesis of CD has been difficult to study, owing to the broad spectrum of typically nonspecific clinical manifestations, the complexity of environmental and genetic factors, the lack of an accurate model of disease, and the limitations of microbiological methods. A more useful and relevant paradigm for the etiology of CD might be based on the idea of a pathogenic microbial community profile and might emphasize the role of interactive sets of microbes, rather than the role of individual organisms. We review how microbes may participate in the pathogenesis of CD and how they may inappropriately activate the mucosal immune system in genetically predisposed individuals.

Crohn Disease↗
PubMed2001

Nutritional strategies to boost immunity and prevent infection in elderly individuals.

Older adults are at risk for malnutrition, which may contribute to their increased risk of infection. Nutritional supplementation strategies can reduce this risk and reverse some of the immune dysfunction associated with advanced age. This review discusses nutritional interventions that have been examined in clinical trials of older adults. The data support use of a daily multivitamin or trace-mineral supplement that includes zinc (elemental zinc, >20 mg/day) and selenium (100 microg/day), with additional vitamin E, to achieve a daily dosage of 200 mg/day. Specific syndromes may also be addressed by nutritional interventions (for example, cranberry juice consumption to reduce urinary tract infections) and may reduce antibiotic use in older adults, particularly those living in long-term care facilities. Drug-nutrient interactions are common in elderly individuals, and care providers should be aware of these interactions. Future research should evaluate important clinical end points rather than merely surrogate markers of immunity.

Aged↗
PubMed2003

[The hemophagocytic syndrome (macrophage activation syndrome)].

The hemophagocytic syndrome (HPS) is an uncommon, often misdiagnosed life-threatening disorder of immune regulation, characterized by a widespread proliferation and multisystemic infiltration of non-malignant histiocytes that undergo uncontrolled hemophagocytosis in bone marrow and/or reticulo-endothelial system. The HPS immune dysfunction consists in a low or absent cytotoxic T and natural killercell activity and in hyperactivation of T lymphocytes and macrophages, with consequent proinflammatory cytokine storm. Clinically, HPS is characterized by high fever, lymphadenopathies, hepato-splenomegaly, liver dysfunction, (pan)cytopenia, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, as well as coagulopathy and neurological manifestations in many cases. A hereditary/primary variant (familial hemophagocytic lymphohistiocytosis) and an acquired/secondary form (reactive HPS) are known. This latter may occur in several disorders, including infections, immunodeficiency states, malignancies, lymphoproliferative and autoimmune diseases. Without treatment, HPS fatally has an unfavourable prognosis. Recently, outcome improvements have been reported, due to better therapeutic strategies. The clinical and pathological features of this syndrome are reviewed.

Histiocytosis, Non-Langerhans-Cell↗
PubMed1979

Matching of chemotherapy to mouse strain and lymphoid tumor type to prevent tumor-induced suppression of specific T- and B-cell functions.

Specific immunological and hematopoietic functions were studied during treatment with antineoplastic agents in mice bearing syngeneic lymphoid tumors: 70Z/2, a B-cell lymphoma of C57BL X DBA/2 F1 (hereafter called (BD2F1) mice; EL4, a T-cell lymphoma of C57BL/6 mice; or J774, a macrophage tumor of BALB/c mice. Both B- and T-lymphocyte function (antibody-forming cells and cell-mediated lymphocyte lympholysis toward alloantigens) were suppressed in spleen cells of mice bearing these tumors. Other hematopoietic functions (granulocyte, macrophage, and megakaryocyte progenitor cells) were variably influenced by growth of these lymphoid tumors. J774 enhanced, but 70Z/2 suppressed, megakaryocyte progenitor cells. J774 and 70Z/2 increased levels of granulocyte-macrophage progenitor cells. EL4, the T-cell lymphoma, did not influence either cell type. Significant variation in strain sensitivity to drug toxicity and drug effectiveness in different tumor-host systems was observed. Increased median survival time with reversal of tumor-induced immune dysfunction, without toxicity to hematopoietic progenitor cells, was realized in two tumor-host-drug combinations. Polyinosinic-polycytidylic acid was effective against J774, while actinomycin D was active against 70Z/2. Mitomycin C effectively reduced tumor load, as evidenced by loss of splenic tumor colony-forming cells for all three tumors. This agent prolonged survival and concomitantly restored immunological responsiveness in hosts immunosuppressed by growth of 70Z/2 or J774. Paralleling tumor reduction with mitomycin C therapy, the splenic hematopoietic progenitor and colony-forming B-cells were reduced in tumor-bearing and tumor-free mice, thus compromising its therapeutic effectiveness. 1-beta-D-Arabinofuranosylcytosine reduced tumor load with marginal toxicity toward hematopoietic progenitor and colony-forming B-cells. However, immune responsiveness was only partially restored, and median survival was not increased. The results presented show the diversity of therapeutic drug effectiveness in increasing mean survival time and influencing other life-sustaining parameters (immunological and hematopoietic functions).

Animals↗