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Atypical fibroxanthoma. Multiple immunohistologic profiles.

The clinical, histologic, and immunohistochemical features of 37 cases of atypical fibroxanthoma (AFX) are presented. Patients ranged in age from 13 to 95 years (mean, 69). Thirty AFXs occurred on the head and neck, and seven lesions developed on the trunk or extremities. The morphologic spectrum varied from a predominant spindle cell pattern with focal cellular pleomorphism to numerous bizarre epithelioid cells with multinucleated giant cells. The spindle cell component in these lesions ranged from 10 to 90% of the constituent cells. Most (31 of 37) AFXs also contained pleomorphic giant cells. Small numbers of S-100-positive dendritic cells were present in 11 cases. Five cases showed variable reactivity with anti-factor-XIIIa. Fifteen (41%) of the AFXs stained for muscle-specific actin or smooth muscle actin and 21 (57%) expressed CD68 (detected with monoclonal KP1), a monocyte-macrophage marker. Reactivity for these antigens was seen in all lesional cell types (spindled, epithelioid, and bizarre). Four immunologic profiles were observed: CD68 only (13 cases), actin only (7 cases), double positives (8 cases), and double negatives (9 cases). No significant differences in staining characteristics were observed in the head and neck versus the trunk and extremity lesions. These results expand the immunohistochemical spectrum of AFX, suggest the concept of heterogenous bimodal "fibrohistiocytic" and "myofibroblastic" phenotypes, and provide further evidence that an integrative, nonalgorithmic approach is necessary in the analysis of these and other spindle cell cutaneous lesions.

Actins↗

Influence of operations with cardiopulmonary bypass on polymorphonuclear leukocyte function in infants.

To determine the effect of operations with cardiopulmonary bypass on the immunologic function of polymorphonuclear leukocytes in infants, we studied polymorphonuclear leukocyte function and immunologic profile in 16 infants undergoing repair of congenital heart lesions. An oxygen/air/high-dose fentanyl anesthetic was used for all patients. Absolute neutrophil count increased significantly (p less than 0.05) after bypass and remained increased 48 hours afterward. Chemotaxis, random migration of polymorphonuclear leukocytes, and phagocytic index were unaffected, but bactericidal capacity decreased significantly immediately after cardiopulmonary bypass and remained decreased 48 hours later. Serum opsonizing capacity to bacterial and fungal antigens was variably altered, and complement factors 3 and 4 decreased significantly after cardiopulmonary bypass. Total hemolytic complement decreased significantly immediately after cardiopulmonary bypass and returned to normal by 48 hours. These data suggest that operations with cardiopulmonary bypass in infants significantly affect the immunologic function of polymorphonuclear leukocytes and result in consumption of complement.

Blood Bactericidal Activity↗

Differential staining of cytoid bodies and skin-limited amyloids with monoclonal anti-keratin antibodies.

The authors have used 5 different monoclonal antikeratin antibodies to study the antigenic profiles of cytoid bodies and skin-limited amyloids. Monoclonal antibodies AE1 (which stains the basal cell layer in normal human epidermis), AE2 (suprabasal layers), AE3 (whole epidermis), EKH4 (lower 2-3 layers), and EKH1 (recognizes all classes of intermediate filaments) were used to stain frozen skin sections by the indirect immunofluorescent or indirect immunoperoxidase technique. Cytoid bodies in lichen planus (LP) and discoid lupus erythematosus (DLE) were strongly stained with AE1, AE3, EKH4, and EKH1 antibodies but were negative with AE2. In contrast, amyloids in lichen amyloidosus and macular amyloidosis were stained strongly with EKH4 but only weakly or not at all with AE1, AE2, AE3, and EKH1. Amyloid associated with epithelial tumors showed closer immunologic profiles to cytoid body. These findings suggest that epidermal keratins are the major precursor substance of skin-limited amyloids as well as cytoid bodies in LP and DLE. Sequential changes in antigenic profiles from basal cells to amyloids through cytoid bodies further suggest that cytoid bodies may represent one of the precursor substances of skin-limited amyloids.

Amyloid↗

[Comparative profile of antinuclear antibodies in Gougerot-Sjögren syndrome with and without diffuse interstitial pulmonary fibrosis].

Eleven patients with an isolated Gougerot-Sjögren syndrome and a diffuse interstitial fibrosis were compared with twenty patients with an isolated Gougerot-Sjögen without pulmonary involvement. Patients with pulmonary fibrosis are younger and the evolution of their dry syndrome is shorter (p less than 0.05) than in patients without fibrosis. The frequency of extra-articular clinical manifestations (except for the lung) is identical in both groups. Antinuclear antibodies are present in 100 p. cent of patients with pulmonary fibrosis. Specific antibodies of soluble nuclear antigens are detected in 64 p. cent of them. This frequency is 55 p. cent in the group without pulmonary fibrosis. The specificities of these antibodies are anti-U1-RNP (3 cases), anti-SS-B (La) (3 cases), anti-SS-A (Ro) (2 cases), non identified (1 case). There was no serum containing antibodies Jo1 or anti-Sm. This immunological profile is identical to the profile found in isolated Gougerot-Sjögren syndromes without pulmonary fibrosis. The search for specific antibodies of soluble nuclear antigens permits to differentiate pulmonary fibrosis secondary to an isolated Gougerot-Sjögren syndrome, from primary diffuse interstitial fibrosis and fibrosis associated to a polymyositis.

Adult↗

Hyperprolactinemia in Sjogren's syndrome: a patient subset or a disease manifestation?

OBJECTIVE: To investigate the prevalence of hyperprolactinemia in patients with primary Sjogren's syndrome (SS), its clinical significance and its implication to our understanding of the disease pathogenesis. MATERIALS AND METHODS: Forty-nine patients with primary SS (44 females and five males) age range 37-66 years were included in this study. All patients underwent clinical assessment for disease manifestations in addition to laboratory assessment for serum prolactin, sex hormones and immunological profile. Fifty healthy subjects (44 females and six males) of matched age were studied as control group. RESULTS: The mean prolactin serum level was significantly higher in SS patients compared to the control group (P < 0.01). This significant difference was persistent after subgrouping the patients and the controls based on their menstrual history. Hyperprolactinemia (>20 ng/ml) was prevalent in 16.3% of SS patients. There was no correlation between serum prolactin levels and hormonal status, autoantibodies as well as systemic manifestations of the disease. CONCLUSION: Patients with primary SS have moderately increased levels of prolactin. Hyperprolactinemia reflects disease pathology rather than being present in a subset of patients. The presence of elevated prolactin levels was not associated with hormonal status, clinical or immunological manifestations of primary SS.

Adult↗

[Purification and standardization of allergens].

Allergen preparations cannot be compared with any other class of drugs. Their compositions are as varied as the raw materials that induce sensitisation and their biological activities are as variable as the individual immunological profiles of patients. They are obtained by extraction and therefore very dependent on the methods used, based on known principles. The multiplicity of the allergens they contain have mostly not yet been characterised and this does not allow individual measurement. Standardisation of the allergen preparations is done mostly by comparison of their overall activity with that of a reference preparation. This is expressed in arbitrary units or in units of biological activity determined on representative mean populations of allergic subjects.

Allergens↗

Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma: an immunologic survival model.

BACKGROUND: Our polyvalent, allogeneic melanoma cell vaccine (MCV) induces immunoglobulin M (IgM) and immunoglobulin G (IgG) class antibodies to a 90-kDa glycoprotein melanoma-associated antigen (MAA). Additionally, MCV induces delayed-type hypersensitivity (DTH) responses that we previously correlated with survival. We hypothesized that early DTH responses to MCV and early humoral responses to the 90-kDa MAA expressed on MCV cells may be predictive of overall survival. We tested this hypothesis by monitoring immunologic profiles in 59 patients with melanoma who were receiving MCV after surgical resection of regional lymph node or soft-tissue metastases. METHODS: Blood was drawn before vaccine administration, biweekly for 6 weeks, and then monthly. DTH to MCV was recorded at 0, 2, 4, and 8 weeks of MCV therapy. Mean antibody titers during the first 6-week interval were calculated. Changes in DTH were calculated as the difference between peak and prevaccine values (delta DTH). RESULTS: At a median follow-up of 75.6 months (range 5-138), univariate analysis assigned prognostic significance to gender (p = 0.046), lymph node involvement (p = 0.024), delta DTH (p = 0.044), mean anti-90-kDa MAA IgG (p = 0.0009), and mean anti-90-kDa MAA IgM (p = 0.0014). In multifactorial analysis, only the three immunologic variables significantly impacted survival (p = 0.046, 0.0005, and 0.0053, respectively). A mathematical model based on delta DTH and mean anti-90-kDa MAA IgG and IgM titers closely approximated the observed individual and overall survival rates. CONCLUSIONS: The correlation between overall survival and initial humoral/cellular immune responses to MCV immunotherapy may be useful in selecting patients most likely to benefit from prolonged adjuvant immunotherapy.

Adolescent↗

Glutathione S-transferases of human lung: characterization and evaluation of the protective role of the alpha-class isozymes against lipid peroxidation.

Glutathione S-transferase (GST) isozymes of human lung have been purified, characterized, quantitated, and, based on their structural and immunological profiles, identified with their respective classes. The tau-, mu-, and alpha-class GSTs represented 94, 3, and 3% activities of total human lung GSTs toward CDNB, respectively, and 60, 10, and 30% of total GST protein, respectively. Both the mu- and the alpha-class GSTs of human lung exhibited heterogeneity. The two mu-class GSTs of human lung had pI values of 6.5 and 6.25 and were differentially expressed in humans. Significant differences were seen between the kinetic properties of these two isozymes and also between the lung and liver mu-class GSTs. The alpha-class GST isozymes of lung resolved into three peaks during isoelectric focusing corresponding to pI values of 9.2, 8.95, and 8.8. All three alpha-class GSTs isozymes had blocked N-termini and were immunologically similar to human liver alpha-class GSTs. Peptide fingerprints generated by SV-8 protease digestion and CNBr cleavage indicated minor structural differences between the liver and the lung alpha-class GSTs. The three alpha-class GSTs of lung expressed glutathione peroxidase activities toward the hydroperoxides of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol, with Km values in the range of 22 to 87 microM and Vmax values in the range of 67-120 mol/mol/min, indicating the involvement of the alpha-class GSTs in the protection mechanisms against peroxidation. All three classes of lung GSTs expressed activities toward leukotriene A4 methyl ester and epoxy stearic acid but the mu-class GSTs had relatively higher activities toward these substrates.

Blotting, Western↗

Immunopathogenesis of Takayasu arteritis.

Takayasu arteritis is a common cause of renovascular hypertension in India. Sensitization to infective agents, particularly mycobacterium tuberculosis or autoimmune disturbances have been incriminated in its pathogenesis. Twenty patients of Takayasu arteritis along with groups of normal individuals, patients of essential hypertension, autoimmune disorders, tuberculosis, and healthy tuberculin reactors were studied. Besides detailed immunological profiles including LE cell phenomenon, serum complement C3 levels, antibodies to single (SS) and double stranded (DS) DNA, rheumatoid factor, lymphocyte subsets, blast transformation to antigens including, phytohemagglutinin, PPD, pokeweed, and purified human aortal antigen (PHAA) were examined. Soluble protein from human aorta was fractionated into 9 peaks by DEASE-52 and Sephadex G-75 chromatography, and 25 micrograms of major protein fraction-II was used for blast transformation study. Blast transformation by PHAA was higher in Takayasu arteritis as compared to all other groups (P < 0.05). Blast transformation to PPD showed wide variation in all the groups, and was significantly higher only in tuberculin reactors as compared to controls. These observations support aortal sensitization to PHAA playing a role in pathogenesis of Takayasu arteritis and do not relate tuberculosis to Takayasu arteritis, at least immunologically. In addition, the ratio of CD-4 positive to CD-8 positive lymphocytes changing in favor of the former and the concomitant increase in B lymphocytes favor the presence of autoimmune disturbances in Takayasu arteritis.

Adolescent↗

Immunosuppressive treatment of chronic non-viral myocarditis.

Inflammatory cardiomyopathy defined as myocarditis associated with cardiac dysfunction, represents a main cause of heart failure. Despite the improvement of diagnostic techniques, a specific standardized treatment of myocarditis is not yet available. The immunohistochemical detection of myocardial HLA up-regulation has been demonstrated useful in the identification of a sub-group of autoimmune inflammatory dilated cardiomyopathy (DCM) in part susceptible to immunosuppression. Recently, in a retrospective study, we defined the virologic and immunologic profile of responders and non-responders to immunosuppressive therapy of active lymphocytic myocarditis and chronic heart failure in patients who had failed to benefit from conventional supportive treatment. Non-responders were characterized by high prevalence (85%) of viral genomes in the myocardium and no detectable cardiac autoantibodies in the serum. Conversely, 90% of responders were positive for autoantibodies, while only 3 (15%) of them presented viral particles at PCR analysis on frozen endomyocardial tissue. With regard to the type of virus involved in non-responders, enterovirus, adenovirus, or their combination was associated with the worst clinical outcome. Hepatitis C virus (HCV) was the only viral agent of our series associated with detectable cardiac autoantibodies, suggesting a relevant immunomediated mechanism of damage by HCV and explaining the relief of myocardial inflammation after immunosuppressive treatment. The assessment of virologic and immunologic features of patients with biopsy-proven inflammatory cardiomyopathy may allow us to identify a specific treatment leading to recovery of cardiac function.

Chronic Disease↗

Clinical profile of lean NIDDM in South India.

The majority (> 80%) of patients with non insulin dependent diabetes mellitus (NIDDM) present in Europe and America are obese. In developing countries like India, most NIDDM (> 60%) are non-obese and many are actually lean with a body mass index (BMI) of < 18.5 and are referred to as 'lean NIDDM'. This paper compares the clinical profile of a cohort of 347 lean NIDDM, with a group of 6274 NIDDM of ideal body weight (IBW) and 3252 obese NIDDM attending a diabetes centre at Madras in South India. The lean NIDDM who constituted 3.5% of all NIDDM patients seen at our centre, had more severe diabetes and an increased prevalence of retinopathy (both background and proliferative), nephropathy and neuropathy. Although a larger percentage of the lean NIDDM patients were treated with insulin, 47% of the males and 53% of the females were still on oral hypoglycaemic agents even after a mean duration of diabetes of 9.2 +/- 8.1 years. Studies of GAD antibodies, islet cell antibodies (ICA) and fasting and stimulated C-peptide estimations done in a small subgroup of the lean NIDDM showed that they were distinct from IDDM patients. More studies are needed on metabolic, hormonal and immunological profile of lean NIDDM seen in developing countries like India.

Adult↗

Murine acariasis. II. Immunological dysfunction and evidence for chronic activation of Th-2 lymphocytes.

The authors describe the immunological profile of BALB/c mice with Mite-Associated Ulcerative Dermatitis (MAUD)-like disease, due to Myocoptes musculinus (Koch 1844) infestation. The disease probably involves allergic mechanisms and is characterized by erythematous and pruritic skin lesions, widespread hair loss, lymphadenopathy, lymphocytopenia, granulocytosis and wasting. Affected individuals had much reduced numbers of pre-B and B cells in bone marrow and B cells in blood; decreased T-cell numbers in peripheral lymphoid organs and blood; hypergammaglobulinaemia with selective increases of IgG1, IgE and IgA, and depletion on IgM and IgG3, the same isotype distribution being detected in splenic plasmocytes; qualitative modifications of the serum antibody reactivity pattern; and increased production of IL-4 with decreased IL-2 production after in vitro polyclonal stimulation of T cells. Taken together, these results suggest that infestation by M. musculinus in BALB/c mice leads to a significant immunological disorder resulting in a T-helper-2 (Th-2) type response, with marked systemic consequences. This pathological condition may thus provide a useful model system for the immunobiological perturbation associated with chronic allergic disease.

Animals↗

Interleukin 1 activity in the acquired immunodeficiency syndrome.

Interleukin 1 (IL-1) is a monocyte-derived mediator that participates in the regulation of various T-lymphocyte activities, among them IL-2 production. Since IL-2 deficiency is a central feature in the immunological profile of the acquired immunodeficiency syndrome (AIDS), the production of IL-1 from peripheral blood monocytes from male homosexuals with AIDS was investigated at the same time as the IL-1 responsiveness of monocyte-depleted mononuclear cells (MDC) from the same patients. The IL-1 was produced by lipopolysaccharide-stimulated monocytes and assayed by the capacity of monocyte supernatants to amplify the proliferation of phytohaemagglutinin-stimulated allogeneic MDC from healthy donors as well as murine thymocytes. The IL-1 responsiveness was measured by measuring the enhancing effect of an IL-1 standard on the proliferative response of patients' MDC. The IL-1 production was not reduced compared to the IL-1 production in a control group, but the IL-1 responsiveness of the patients' MDC was depressed. The results indicate that depressed IL-1 production is not one of the immunological disturbances in AIDS, but that the T-lymphocyte accessory properties of IL-1 are affected.

Acquired Immunodeficiency Syndrome↗

Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3-oxododecanoyl)-L-homoserine lactone as immune modulators.

Comparative immune modulatory activity for a range of synthetic analogues of a Pseudomonas aeruginosa signal molecule, N-(3-oxododecanoyl)-l-homoserine lactone (3O, C(12)-HSL), is described. Twenty-four single or combination systematic alterations of the structural components of 3O, C(12)-HSL were introduced as described. Given the already defined immunological profile of the parent compound, 3O, C(12)-HSL, these compounds were assayed for their ability to inhibit murine and human leucocyte proliferation and TNF-alpha secretion by lipopolysaccharide (LPS) stimulated human leucocytes in order to provide an initial structure-activity profile. From IC(50) values obtained with a murine splenocyte proliferation assay, it is apparent that acylated l-homoserine lactones with an 11-13 C side chain containing either a 3-oxo or a 3-hydroxy group are optimal structures for immune suppressive activity. These derivatives of 3O, C(12)-HSL with monounsaturation and/or a terminal nonpolar substituent on the side chain were also potent immune suppressive agents. However, structures lacking the homoserine lactone ring, structures lacking the l-configuration at the chiral center, and those with polar substituents were essentially devoid of activity. The ability of compounds selected from the optimal activity range to modulate mitogen-driven human peripheral blood mononuclear cell proliferation and LPS-induced TNF-alpha secretion indicates the suitability of these compounds for further investigation in relation to their molecular mechanisms of action in TNF-alpha driven immunological diseases, particularly autoimmune diseases such as psoriasis, rheumatoid arthritis, and type 1 (autoimmune) diabetes.

Adjuvants, Immunologic↗

Immunological investigation and immunotherapy in patients operated on for breast carcinoma.

The tumor-host relationship is an essential factor in the onset, development, and recovery from malignancies. A basic consideration in the treatment of cancer patients must therefore be to understand this relationship and attempt to modify it in order to favor the host. We here discuss the results of a study of the immunologic status of 91 breast cancer patients. The use of a battery of tests with five subcutaneous hypersensitivity antigens allowed us to detect some differences in the immunological profiles of patients with or without lymph node involvement. The effect of an immunostimulant fraction prepared from Corynebacterium granulosum, P40 is also analyzed. This fraction significantly modifies tumoral recurrence in DMBA-induced mammary cancers in the Sprague Dawley rat, causes regression of mammary permeation nodules following in situ injection and modifies the cutaneous reactions of one-half of the anergic breast cancer patients although regular re-challenge is still necessary.

Adenocarcinoma↗

Evaluation of risk and diagnostic value of quantitative assays for anti-Toxoplasma gondii immunoglobulin A (IgA), IgE, and IgM and analytical study of specific IgG in immunodeficient patients.

To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects, we assayed immunoglobulin A (IgA) and IgE antibodies by means of immunocapture (IC) tests, with revelation done by using a suspension of T. gondii (ICT). We also carried out a simultaneous analytical study of IgG antibodies on cellulose acetate membranes by using the comparative immunological profile method and an enzyme-linked immunofiltration assay (ELIFA). A total of 1,238 samples (serum, cerebrospinal fluid, and aqueous humor from 318 patients) were tested. IgA and IgE antibodies were detected in all heart, kidney, and liver transplant recipients with clinical manifestations of toxoplasmosis; IgA was detected in the aqueous humor of a patient with chorioretinitis. In patients with AIDS-related toxoplasmosis, including the cerebral form, IgA and IgE antibodies or a significant modification of ELIFA IgG values were observed in 38, 19, and 25% of patients, respectively. IgM was detected by ICT only in 12% of patients and aided the diagnosis in 1 of 71 patients. IC tests for specific IgA and IgE alone and combined with ELIFA were positive in 39 and 46% of patients who developed clinical toxoplasmosis, respectively. In a serial study of 16 patients in whom at least one of these three tests was positive, a significant immunological signal sometimes preceded clinical onset by 1, 6, and even 17 months. Similarly, in a group of human immunodeficiency virus-infected patients with evidence of previous exposure to T. gondii but no clinical manifestations, IgA, IgE, and IgA and/or IgE antibodies were detected in only 11, 4, and 12% of patients, respectively. These two situations point to peripheral T. gondii reactivation. IgA and IgE emerged as interesting markers of the risk of toxoplasmosis in immunodepressed patients. They may also provide valuable assistance in the diagnosis of toxoplasmosis, especially because tests for specific IgM are disappointing. However, at least one in two patients with toxoplasmosis showed no detectable immunological reaction, suggesting that this polyisotypic approach should be combined with other noninvasive methods such as gene amplification.

AIDS-Related Opportunistic Infections↗

[Immunologic aspects of ankylosing spondylarthritis].

The immunological profile of 63 men, 53 of whom were carriers of the HLA B27 antigen, and 10 of whom were not, all of whom suffered from ankylosing spondylarthritis (ASP) which was either quiescent or subject to exacerbations, were studied: lymphocytic colonies, quantity determination of serum proteins, investigations of auto-immune antibodies. Following a discussion of the techniques, the results are presented and compared with those obtained in healthy subjects. No significant difference was revealed between the averages obtained for the results on the patients and the controls, nor as regards the B and T lymphocytes, the IgG, IgA, IgM immunoglobulins, the C3 fraction of the complement, or orosomucoid. The haptoglobin and alpha-antitrypsin rates increased significantly in the patients. Tests for the auto-immune antibodies were always negative. The results are compared to other, often contradictory, studies which have already been published. These authors conclude that the ASP in question does not seem to be an immunological disease.

Adult↗

[The role of gamma-delta T-lymphocyte subtypes in normal and pathologic conditions].

In the review data about origin, spreading in the organism, differentiation, physiologic sense, role in diversity of pathologic processes, and also pharmaco- and immunocorrection's probable foundations of T-lymphocyte's new population with T cell receptor (TcR) gamma delta (TL gamma delta) are resumed. In the phylogenesis TL gamma delta are supposed to be older than T lymphocytes with TcR alpha beta. The conclusion is based upon domination of this lymphocyte population at gestation's early stage and huge representation of pseudogenes in the DNA region that encodes TcR structure of TL gamma delta. A morphological and functional resemblance of the given population with natural killer cells is underlined. It is paid attention to wide representation of TL gamma delta in the periphery tissues, poverty of TcR diapason that may evidence about postdifferentiation's process of TL gamma delta to be accomplished due to TcR genes rearrangement. This process appears to supply the enhancement of antigen-specific TL gamma delta in foreign agent's inculcation. A maturation process and probable mechanisms of these lymphocytes education in thymus is described. A classification of TL gamma delta depending on TcR structure and cytokine profile of the lymphocytes that subdivides them on T-helper/cytotoxic (Vg9/Vd2 phenotype) and cytotoxic/suppressor (Vd1 or Vd3 phenotype) was proposed. In the review the role of TL gamma delta in mucous immunity supporting and possible participating in systemic regulation of the immune response is emphasized. A physiologic role of TL gamma delta, namely ability to identify non-protein antigens (lipopolysaccharides, polyphosphates, glycolipids) and heat shock proteins, is also described. Evidences about uncertainty of incomplete phagocytosis phenomenon in vivo in case of TL gamma delta's normal function are given. Particularly it is made out that these lymphocytes are able to activate inducible NO-synthase in the macrophages that enhances their phagocytic activity in tens time. A function of these lymphocytes in defense against infection of bacterial, viral, protozoa, fungal origin, and also in tumor growth and autoimmune diseases is represented. Methods of specific therapeutic influence upon TL gamma delta, both pharmacological (pamidronat, 2,3-diphosphoglyceric acid) and immunologic profile (monoclonal antibodies conjugated with cytotoxic agent) are given.

Animals↗