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K E Balashov

Publications and source records attributed to K E Balashov.

At least 19 recordsLinked to original sources
PubMed2000

Defective regulation of IFNgamma and IL-12 by endogenous IL-10 in progressive MS.

BACKGROUND: MS is a chronic inflammatory disease of the CNS postulated to be a Th1 type cell-mediated autoimmune disease. There is increased interferon-gamma (IFNgamma) secretion in MS, and IFNgamma administration induces exacerbations of disease. IFNgamma expression is closely regulated by a number of cytokines produced by different cells of the immune system. Interleukin-12 (IL-12) is a major factor leading to Th1-type responses, including IFNgamma secretion, and there is increased secretion of IL-12 in MS. IL-10 is a potent inhibitor of both IL-12 and IFNgamma expression. METHODS: The authors investigated cytokine production and proliferative responses of peripheral blood mononuclear cells stimulated with soluble anti-CD3 in healthy controls and patients with stable relapsing-remitting MS or progressive MS. RESULTS: The authors found that T cell receptor-mediated IFNgamma and IL-10 secretion were increased in progressive MS, whereas IL-4 and IL-2 secretion and lymphocyte proliferative responses were normal. Anti-IL-12 antibody suppressed raised IFNgamma in progressive MS but did not affect raised IL-10. In addition, neutralization of endogenous IL-10 upregulated IFNgamma in controls but not progressive MS. IL-10 was produced by CD4+ cells whereas IFNgamma was produced by both CD4+ and CD8+ cells. There were no differences in IL-10 receptor expression in MS patients. CONCLUSIONS: These abnormalities in IL-10 regulation were not seen in the relapsing-remitting form of MS. Thus, the defect in regulation of both IL-12 and IFNgamma production by endogenous IL-10 in progressive MS could be an important factor involved in the transition of MS from the relapsing to the progressive stage and has implications for treating MS patients with exogenous IL-10.

Adult↗
PubMed1999

CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions.

Multiple sclerosis (MS) is a T cell-dependent chronic inflammatory disease of the central nervous system. The role of chemokines in MS and its different stages is uncertain. Recent data suggest a bias in expression of chemokine receptors by Th1 vs. Th2 cells; human Th1 clones express CXCR3 and CCR5 and Th2 clones express CCR3 and CCR4. Chemokine receptors expressed by Th1 cells may be important in MS, as increased interferon-gamma (IFN-gamma) precedes clinical attacks, and IFN-gamma injection induces disease exacerbations. We found CXCR3(+) T cells increased in blood of relapsing-remitting MS, and both CCR5(+) and CXCR3(+) T cells increased in progressive MS compared with controls. Furthermore, peripheral blood CCR5(+) T cells secreted high levels of IFN-gamma. In the brain, the CCR5 ligand, MIP-1alpha, was strongly associated with microglia/macrophages, and the CXCR3 ligand, IP-10, was expressed by astrocytes in MS lesions but not unaffected white matter of control or MS subjects. Areas of plaque formation were infiltrated by CCR5-expressing and, to a lesser extent, CXCR3-expressing cells; Interleukin (IL)-18 and IFN-gamma were expressed in demyelinating lesions. No leukocyte expression of CCR3, CCR4, or six other chemokines, or anti-inflammatory cytokines IL-5, IL-10, IL-13, and transforming growth factor-beta was observed. Thus, chemokine receptor expression may be used for immunologic staging of MS and potentially for other chronic autoimmune/inflammatory processes such as rheumatoid arthritis, autoimmune diabetes, or chronic transplant rejection. Furthermore, these results provide a rationale for the use of agents that block CCR5 and/or CXCR3 as a therapeutic approach in the treatment of MS.

Adult↗
PubMed1998

Identification of a T cell subset capable of both IFN-gamma and IL-10 secretion in patients with chronic Borrelia burgdorferi infection.

A novel population of both IFN-gamma- and IL-10-secreting human T cells that differentiate in the presence of exogenous IL-12 in vitro has recently been described. Whether this T cell population exists in vivo is unknown. Borrelia burgdorferi, the etiologic agent of Lyme disease, can induce a chronic infection in the presence of a vigorous humoral immune response. We established T cell lines specific for B. burgdorferi and tetanus toxoid from subjects with chronic B. burgdorferi infection and healthy controls in limiting dilution experiments and assessed proliferation and cytokine secretion. As expected, higher frequencies of B. burgdorferi-specific precursor T cells were observed in Lyme patients compared with controls. In both groups of subjects, T cell lines specific for B. burgdorferi secreted high amounts of IFN-gamma. However, in patients with Lyme disease, 27% of T cell lines secreted not only IFN-gamma but also IL-10, which was only observed in 0.6% of B. burgdorferi-reactive T cell lines generated from controls and in none of the tetanus toxoid-reactive T cell lines generated from either Lyme patients and controls. Single cell PHA cloning confirmed that both cytokines were secreted from one clonally expanded precursor cell. Whole mononuclear cells from B. burgdorferi-infected individuals, but not from controls, secreted IL-12. Moreover, neutralizing anti-IL-12 mAbs inhibited the generation of the IFN-gamma/IL-10 population. These data demonstrate that this novel population of IL-12-induced IFN-gamma/IL-10-secreting T cells is generated in response to chronic B. burgdorferi infection.

Adult↗
PubMed1998

Seasonal variation of interferon-gamma production in progressive multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. There is increased interferon (IFN)-gamma secretion in MS patients in vitro, and IFN-gamma administration induces exacerbations of disease suggesting a link between IFN-gamma and disease activity. We observed significantly increased IFN-gamma production in the autumn and winter months compared with the spring and summer months in chronic progressive MS, and this increase was linked to endogenous interleukin (IL)-12 production. Increased seasonal IFN-gamma was not observed in normal control subjects, and there were no seasonal changes in IL-10 in progressive MS. These results suggest a potential environmental link between dysregulated IFN-gamma production and MS disease progression and pathogenesis.

Cells, Cultured↗
PubMed1997

Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system postulated to be a cell-mediated autoimmune disease in which interferon gamma (IFN-gamma) plays an important role. There is increased IFN-gamma secretion in MS, and IFN-gamma administration induces exacerbations of disease. We found that interleukin 12 (IL-12) was responsible for raised IFN-gamma secretion in MS as anti-IL-12 antibodies reversed raised anti-CD3-induced IFN-gamma in MS patients to normal levels. Furthermore, we found a marked increase in T cell receptor-mediated IL-12 secretion in progressive MS patients vs. controls (24.8 +/- 7.7 pg/ml vs. 1.5 +/- 1.0 pg/ml, P = 0.003) and vs. relapsing-remitting patients (3.7 +/- 1.4 pg/ml, P < 0.05). Investigation of the cellular basis for raised IL-12 demonstrated that T cells from MS patients induced IL-12 secretion from non-T cells, and that T cells from MS patients could even drive non-T cells from normal subjects to produce increased IL-12. Anti-CD40 ligand antibody completely blocked IL-12 secretion induced by activated T cells, and we found increased CD40 ligand expression by activated CD4+ T cells in MS patients vs. controls. The CD40 ligand-dependent Th1-type immune activation was observed in the progressive but not in the relapsing-remitting from of MS, suggesting a link to disease pathogenesis and progression and providing a basis for immune intervention in the disease.

Adult↗
PubMed1997

Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: increased interleukin-4 production and associated eosinophilia.

Multiple sclerosis (MS) is postulated to be a Th1-type cell-mediated autoimmune disease. Thus therapies that decrease T cell interferon (IFN)-gamma production or increase interleukin (IL)-4 production would be expected to have an ameliorating effect on MS. Some progressive MS patients receiving pulse cyclophosphamide therapy developed peripheral blood eosinophilia. We investigated whether cyclophosphamide-treated patients had immune deviation toward Th2 responses. We measured cytokine production in patients receiving either monthly intravenous methylprednisolone (MP), intravenous cyclophosphamide plus methylprednisolone (CY/MP), methotrexate, IFN-beta1b, in untreated MS patients, and in healthy controls. Minimal IL-4 was secreted in untreated patients (129 +/- 62 pg/ml), methotrexate-treated patients (99 +/- 79 pg/ml), and healthy controls (50 +/- 13 pg/ml). A marked increase in IL-4 was observed in CY/MP patients (1,503 +/- 291 pg/ml). Patients treated with MP (418 +/- 160 pg/ml) or IFN-beta1b (425 +/- 167 pg/ml) showed small increases. Eosinophilia in CY/MP-treated patients (6.0 +/- 0.7%) correlated with increased IL-4. IL-10 production was also increased in CY/MP-treated patients. Both CY/MP- and MP-treated groups had decreased production of IFN-gamma compared with untreated MS. These findings demonstrate pronounced immune deviation favoring Th2-type responses after pulse cyclophosphamide therapy.

Adult↗
PubMed1995

Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis.

The autologous mixed lymphocyte reaction (AMLR) involves the activation of T cells by autologous antigen presenting cells. Cells are generated during the course of the AMLR that have suppressive properties in vitro. In the present study we investigated the induction of CD8+ T cells in the AMLR with suppressive properties and the mechanism by which these cells downregulate in vitro proliferative responses. Purified CD8+ but not CD4+ T cells activated in the AMLR in conditioned medium inhibited proliferation of autologous T cells by anti-CD3 or PPD. Nonactivated CD8+ T cells did not suppress. The CD8+ T cells activated in the AMLR in the presence of conditioned medium (CD8+ Tact) were CD11b negative and were noncytotoxic. The inhibitory effect of CD8+ Tact cells was completely abrogated by anti-IFN-gamma antibody, but not by anti-IL-4, anti-IL-10, or anti-TGF-beta antibody. The induction of CD8+ Tact cells in the AMLR was blocked by anti-IL-2 or by anti-GM-CSF antibody and the combination of these two recombinant cytokines could support the induction of suppressive CD8+ Tact cells. CD8+ Tact cells were defective in patients with chronic progressive multiple sclerosis (MS) as compared to patients with relapsing-remitting MS or normal controls. Our studies provide a basis for understanding the mechanism of suppression by human CD8+ T cells in terms of specific cytokines, and demonstrate the potential importance of these cells in a human autoimmune disease as their function is defective in patients with progressive MS.

CD8-Positive T-Lymphocytes↗
PubMed1992

Application of anti-CD3-treated lymphocytes as stimulator cells in human autologous mixed lymphocyte cultures for generation of autorestricted CD8+ suppressor T cells.

The purpose of the present study was to investigate the application of anti-CD3-treated lymphocytes as stimulator cells in human one-way autologous mixed lymphocyte cultures (MLC) for the generation of suppressor cells. MLC-activated CD4-CD8+ CD16- T cells were non-cytotoxic, while they down-regulated the proliferation of autologous (but not allogeneic) responder lymphocytes in allogeneic test MLC.

Antibodies, Monoclonal↗
PubMed1991

Different conditions for generation of non-cytotoxic autorestricted CD4-CD8+ human suppressor T cells and allospecific cytotoxic T lymphocytes in one-way mixed lymphocyte cultures: the role of adherent mononuclear cells.

The purpose of the present study was to investigate the role of adherent mononuclear cells (AMC) in generation of suppressor T lymphocytes (T-Lph) in one-way allogeneic mixed lymphocyte cultures (MLC). Alloantigen-specific cytotoxic T-Lph were generated in MLC predominantly in the presence of stimulator AMC, but not responder AMC. The presence of responder AMC and the absence of stimulator AMC were optimal conditions for generation of non-cytotoxic (through the whole duration of MLC) suppressor T-Lph. These CD4-CD8+ suppressor T-Lph were allononspecific but autorestricted (with responders in test MLC).

CD4 Antigens↗
PubMed1991

The role of T lymphocytes in the immunotherapy of tumours.

The interactions of tumour cells with membrane molecules of T-cell subsets, as well as methods directed towards the enhancement of antitumour immunity, are reviewed in this paper. Special attention is given to the cytotoxic function of lymphokine-activated tumour-infiltrating lymphocytes, to tumour-specific suppressor T cells, and to various causes of decreased expression of histocompatibility antigens on the surface of tumour cells. The different mechanisms underlying selective antitumour immunodeficiencies and possible approaches to the correction of immunodeficiency, to the enhancement of tumour immunogenicity, and to specific immunotherapy are considered in more detail.

Adjuvants, Immunologic↗
PubMed1990

[Characteristics of the set-up of the lymphocyte blast transformation reaction using whole blood].

The authors analyze the specific features of the technique of lymphocyte blastogenesis test (LBGT) with whole blood and of interpreting its results in examinations of healthy donors, patients with hypogammaglobulinemia, chronic bronchitis or pneumonia, and bronchial asthma. The suggested LBGT variant is a sensitive and reproducible technique fit for assessing the immunity status, making use of small volumes (up to 0.1 ml) of the blood; it is recommended for clinical examinations and mass immunologic screenings.

Adult↗
PubMed1990

[Immunologic status in autonomic prosopalgias].

The authors describe the results of immunological examination of patients suffering from vegetative prosopalgias. A study was made of the initial status of immunity and of its dynamics after treatment. The majority of patients manifested an increase of immunoglobulin A concentration and activation of local humoral immunity. The treatment brought about a reduction of immunoglobulin A concentration in blood serum.

Adult↗
PubMed1990

[Study of cellular immunity and the opioid peptide system in patients with multiple sclerosis].

Twenty-five patients with chronic progressing multiple sclerosis were examined for the content of beta-endorphin in blood serum, supernatants of activated lymphocytes and CSF by RIA. At the same time the parameters of cellular immunity were appraised. Different relations were discovered between cellular immunity and the content of beta-endorphin in biological fluids which may play a material part in the pathogenesis of multiple sclerosis.

Adult↗
PubMed1989

[Characteristics of cellular immunity in multiple sclerosis].

In 30 patients with definite multiple sclerosis a combined clinicoimmunological investigation was performed. The results of estimation of T-lymphocyte subpopulations by means of flow cytometry and monoclonal antibodies; of proliferative responses to PHA, PWM and Con A, to PHA with autoserum; of synthesis and reception of IL-2 containing material is discussed. A hypothesis of a cyclic course of the immunopathologic process is suggested (autoimmune and immunodeficiency stages).

Adult↗
PubMed1989

[Immunologic aspects of migraine headaches and autonomic prosopalgias].

The paper presents the results of an immunological screening of patients with facial vegetative neuralgia, Horton's syndrome, and migraines prior to and following therapy. The patients with migraines were found to have an activated local humoral immunity. Those from all the groups showed lower serum immunoglobulin A concentrations after therapeutic interventions.

Adult↗