Biomedical subjects

T K Kondratieva

Publications and source records attributed to T K Kondratieva.

8 recordsLinked to original sources

PubMed2004

Lung cell responses to M. tuberculosis in genetically susceptible and resistant mice following intratracheal challenge.

One approach to study the role of distinct cellular mechanisms in susceptibility/resistance to tuberculosis (TB) is to compare parameters of response to infection in the lungs of mouse strains exhibiting genetically determined differences in TB susceptibility/severity. Interstrain differences in antimycobacterial macrophage reactions, T cell responses & inflammation in the lungs of TB-susceptible I/St, TB-resistant A/Sn and (I/St x A/Sn)F1 mice were analysed following intratracheal inoculation of 103 CFUs of M. tuberculosis H37Rv. The antimycobacterial responses in the lungs of susceptible I/St mice were characterized by: (i) increased inflammatory infiltration by all major immune cell subsets; (ii) decreased type 1 cytokine production; (iii) impaired antimycobacterial activity of lung macrophages; (iv) unusually high proliferation of lung T lymphocytes. Differences in several parameters of anti-TB immunity between susceptible and resistant mice corresponded well to the polygenic pattern of TB control previously established in this mouse model. Importantly, lung macrophages isolated from noninfected mice were unable to respond to IFN-gamma by increasing their mycobactericidal function, but between weeks 3 and 5 of the infection this capacity developed in all mice. However, by this time point susceptible but not resistant mice demonstrated a pronounced decrease in IFN-gamma production by lung cells. This chain of events may explain the inability of I/St mice to control both early and chronic TB infection.

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PubMed2000

Comparative analysis of T lymphocytes recovered from the lungs of mice genetically susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease.

Genetic control of susceptibility to tuberculosis (TB) is being intensively studied, and immune responses to mycobacteria are considerably well characterized. However, it remains largely unknown which parameters of response distinguish resistant and susceptible TB phenotypes. Mice of I/St and A/Sn inbred strains and (A/Sn x I/St)F(1) hybrids were previously categorized as, respectively, susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease. In the present work we compared parameters of lung T cell activation and response following M. tuberculosis challenge. In all mice, the disease progression was accompanied by a marked accumulation in the lungs of activated CD4(+) (CD44(high)/CD45RB(low)) and CD8(+) (CD44(high)/CD45RB(+)) T cells capable of secreting IFN-gamma and of activating macrophages for NO production and mycobacterial growth inhibition. However, significantly more CD8(+) T cells were accumulated in the lungs of resistant A/Sn and F(1) compared with I/St mice. About 80% A/Sn and F(1) CD8(+) cells expressed CD44(high)/CD45RB(+) phenotype, while about 40% I/St CD8(+) cells did not express CD45RB marker at week 5 of infection. In contrast, in susceptible I/St mice lung CD4(+) cells proliferated much more strongly in response to mycobacterial sonicate, and a higher proportion of these cells expressed CD95 and underwent apoptosis compared with A/Sn cells. Unseparated lung cells and T cells of I/St origin produced more IL-5 and IL-10, respectively, whereas their A/Sn and F1 counterparts produced more IFN-gamma following infection. F(1) cells overall expressed an intermediate phenotype between the two parental strains. Such a more balanced type of immune reactivity could be linked to a better TB defense.

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PubMed2000

Characterization of T cell clones derived from lymph nodes and lungs of Pseudomonas aeruginosa-susceptible and resistant mice following immunization with heat-killed bacteria.

Pseudomonas aeruginosa-resistant BALB/c and susceptible C57Bl/6 (B6) mice were immunized with heat-killed Pseudomonas either in the foot pad or via the trachea, and panels of Pseudomonas-specific T cell clones were developed from lymph nodes and lungs. All clones from either strain, whether of lymph node or lung origin, were CD3+CD4+CD8-TCRalphabeta+. The efficacy of cloning from lymph node cells was comparable between BALB/c and B6 mice. All lymph node BALB/c clones proliferated in response to Pseudomonas antigen in a dose-dependent manner, and this response was MHC class II-restricted. Vigorous proliferation by a considerable proportion of B6 T cell clones occurred in the absence of specific antigen. Lymph node clones from either strain could be categorized as either Th1 or Th0 on the basis of interferon-gamma (IFN-gamma)/IL-4 production. In either mouse strain the efficacy of cloning from lung tissue was substantially lower than from lymph nodes, but the efficacy of cloning from BALB/c compared with B6 lungs was higher. Four lung T cell clones from BALB/c and two from B6 mice were expanded for further analyses, and an interstrain difference was observed in cytokine production. Both B6 lung T cell clones were Th1-like and produced IFN-gamma but not IL-4 and IL-10, whereas four BALB/c lung T cell clones were Th2-like and produced IL-4 and IL-10 but not IFN-gamma. These observations suggest that differences in the CD4+ Th response in the lung may contribute to differences among inbred mouse strains in the level of resistance to bronchopulmonary Pseudomonas infection.

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PubMed1998

A new approach to obtain Lyb5-specific antiserum.

A new approach to obtain antiserum specific for Lyb5.2 allotype, was developed. Mice of DBA/2 inbred strain, bearing Lyb5.1 allotype, were made unresponsive to cellular antigens of Lyb5-CBA/N mice by specific tolerance induction. These tolerant recipients were further immunized with suspensions of splenocytes from CBA mice which contain Lyb5.2 + B lymphocytes. Thus obtained Lyb5.2-specific antiserum was cytotoxic for 25-30% of CBA or BALB/c (both Lyb5.2 + allotype) but not for CBA/N spleen cells. When splenocytes of BALB/c mice preimmunized with polyvinylpyrrolidone (T-independent type 2 antigen) were treated with this antiserum, 50% decrease in numbers of antibody-forming and antigen-induced non-specific immunoglobulin-forming cells was documented. We conclude that, during humoral immune response to T-independent type 2 antigen, not only antibody-forming cells but also non-specific immunoglobulin-forming cells are recruited from the Lyb5 + B cell pool.

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PubMed1995

In vitro and in vivo T cell responses in mice during bronchopulmonary infection with mucoid Pseudomonas aeruginosa.

In vitro and in vivo T cell responses were determined during the course of bronchopulmonary infection with mucoid Pseudomonas aeruginosa. T cell responses were compared in two inbred mouse strains, namely BALB/c mice, which are resistant to the establishment of chronic bronchopulmonary Ps. aeruginosa infection, and C57Bl/6 mice, which have high numbers of bacteria in the lungs through 14 days post-infection. Unseparated lung cells and lung T cells from BALB/c mice exhibited significantly higher in vitro proliferative responses to both heat-killed Ps. aeruginosa and concanavalin A (Con A) than cells from C57Bl/6 mice through 20 days post-intratracheal infection with 10(4) colony-forming units (CFU) Ps. aeruginosa. Proliferation of unseparated lung cells but not lung T cells from BALB/c mice infected 6 days previously with 10(5) CFU Ps. aeruginosa was suppressed in response to Con A; these cells were unresponsive to specific antigen. Suppression of lymphocyte proliferation in the lungs of C57Bl/6 mice infected with 10(4) CFU Ps. aeruginosa and in BALB/c mice infected with 10(5) CFU was found to be mediated by adherent lung cells via the production of nitric oxide and prostaglandins. Determination of in vivo T cell-mediated responses in infected mice demonstrated that resistant BALB/c mice had high DTH and low Pseudomonas-specific antibody responses, while C57Bl/6 mice had low DTH and high antibody levels, in particular, IgG2b and IgM.

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PubMed1989

Recovery from polyclonal tolerance: simulation analysis.

Mathematical model of immunological tolerance was applied to polyclonal B cell tolerance induced in mice by treatment with bacterial lipopolysaccharide (LPS) followed by the application of cyclophosphamide (CY). Satisfactory simulation results were obtained with the life-span of lymphocytes shorter than the experimentally observed one. It could be assumed that the massive decrease of lymphocyte population in polyclonal tolerance would elicit a compensatory reaction. Therefore it was postulated that some kind of feedback mechanism increased the influx of B lymphocytes. Having this factor included in the model, satisfactory agreement of the simulation results with experimental data was obtained for experimentally determined life-span of B cells.

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PubMed1988

Polyclonal B cell anergy induced by bacterial lipopolysaccharide and cyclophosphamide.

Tolerogenic treatment of mice by successive injections of lipopolysaccharide (LPS) from E. coli or S. marcescens and cyclophosphamide (CY) decreased both the specific and polyclonal responses to tolerogen and to irrelevant LPS from Br. abortus as well as the specific immune response to sheep red blood cells. Splenocytes of tolerant mice were unresponsive to polyclonal challenge when transferred to irradiated syngeneic recipients. Spleen cells or blood serum from tolerant mice did not suppress the polyclonal response of intact mice to LPS. Possible reasons for the polyclonal B cell anergy were analyzed.

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PubMed1985

Studies on lipopolysaccharide-induced polyclonal B cell activity in mice tolerized by sheep red blood cells and cyclophosphamide.

The polyclonal immune response was induced in untreated mice and mice treated with cyclophosphamide by the administration of lipopolysaccharide from E. coli or S. marcescens. The number of cells forming antibodies to sheep red blood cells and to trinitrophenyl, and of cells producing immunoglobulins increased. The administration of LPS to mice pretreated with SRBC and CY (tolerant mice) considerably reduced the number of anti-SRBC AFC in comparison with the controls. The tolerogenic treatment did not change the number of anti-TNP AFC and IPC. Analogous results were obtained in genetically athymic (nude) mice and in B mice (thymectomized, lethally irradiated and reconstituted with embryonic liver cells). The results suggest that a deletion or a temporary inactivation of a fraction of the antigen-specific B cells occurs in tolerant mice. This inactivation cannot be explained by the absence of expression of surface immunoglobulins on B cells nor by the activity of suppressor T cells.

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