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Biomedical subjects

K Hála

Publications and source records attributed to K Hála.

At least 19 recordsLinked to original sources
PubMed2001

DNA vaccination against v-src oncogene-induced tumours in congenic chickens.

DNA vaccination is particularly efficient for induction of cytotoxic T-lymphocyte (CTL) response. In our experiments, we used MHC(B) congenic chicken lines CB and CC (regressors and progressors of v-src-induced tumours, respectively) and a mutated, non-oncogenic v-src gene construct as the DNA vaccine. A high degree of vaccine protection against oncogenic v-src challenge was achieved in the CB line chickens. CTL response was demonstrated in vitro and by adoptive transfer of immune cells to the syngeneic host and to the CC line chickens rendered tolerant to CB cells. In the CC line chickens we observed tumour growth retardation after a low-dose DNA vaccination administered to immature recipients while higher amounts of DNA vaccine in immunocompetent chickens exerted an enhancing effect.

Adoptive Transfer↗
PubMed1998

Inhibition of the development of spontaneous autoimmune thyroiditis in the obese strain (OS) chickens by in vivo treatment with anti-CD4 or anti-CD8 antibodies.

The involvement of CD4+ and CD8+ T cells in pathogenesis of spontaneous autoimmune thyroiditis (SAT) in obese strain (OS) chickens has not been studied in depth until now. We depleted CD4+ or CD8+ T cells in OS chickens by treatment with murine monoclonal anti-CD4 or anti-CD8 antibodies at 3 day intervals beginning at hatching. The birds were killed at 19-25 days of age. Treatment with anti-CD4 antibody completely prevented SAT development, while treatment with anti-CD8 antibody partially inhibited SAT. These results show the critical role of CD4+ T cells in the development of SAT in OS chickens, and indicate that CD8+ T cells are also involved in SAT pathogenesis.

Age Factors↗
PubMed1996

Prevention of spontaneous autoimmune thyroiditis in the obese strain (OS) chickens by treatment with a monoclonal anti-CD4 antibody.

Untreated control OS chickens develop spontaneous autoimmune thyroiditis (SAT). In contrast, OS chickens treated with a monoclonal anti-CD4 antibody failed to develop SAT. The preventive effect of anti-CD4 antibody on SAT was associated with the marked depletion of CD4+ T-cells by anti-CD4 treatment. These results indicate that CD4+ T-cells play a crucial role in SAT of OS chickens.

Animals↗
PubMed1995

Preferential TCR V beta 1 gene usage by autoreactive T cells in spontaneous autoimmune thyroiditis of the obese strain of chickens.

We studied T cell receptor variable beta (TCR V beta) gene usage by autoreactive T cells in spontaneous autoimmune thyroiditis (SAT) of obese strain (OS) chickens. Chicken alpha beta T cells may express either V beta 1 or V beta 2 genes, the products of which can be recognized by TCR2 and TCR3 monoclonal antibodies, respectively. Selective depletion of V beta 1+ or V beta 2+ T cells in OS chickens was accomplished by repeated injections of TCR2 or TCR3 antibodies into embryonic and 1-3-week-old chickens. The birds were killed at 20 days of age and their spleens and thyroid glands evaluated by immunohistochemistry. We found that V beta 1+ T cells preferentially infiltrated OS chicken thyroid glands. Antibody treatments resulted in a 41% reduction in frequency of V beta 1+, and a 87% reduction of the frequency of V beta 2+ cells in the circulation, and in a profound decrease of the respective T cells in spleens and thyroid glands. Selective suppression of V beta 1+ T cells partially inhibited SAT development in that thyroid-infiltrating cells and destruction of thyroid follicles were reduced by more than 50%. Thyroglobulin autoantibody serum levels were also reduced in V beta 1+ T cell-depleted OS chickens, whereas selective depletion of V beta 2+ T cells did not inhibit SAT development. These findings indicate preferential TCR V beta 1 gene usage by autoreactive T cells in SAT of OS chickens.

Animals↗
PubMed1994

src-specific immunity in inbred chickens bearing v-src DNA- and RSV-induced tumors.

The growth pattern (progression/regression) of v-src DNA- and Rous sarcoma virus (RSV)-induced tumors was analogous on a panel of inbred chicken lines. The decisive role of the major histocompatibility complex [Mhc(B)] alleles in resistance to the progression of these tumors was formally proved in segregating backcross populations. The immune mechanism of tumor regression was demonstrated by both in vivo and in vitro assays. A protective effect of v-src-specific immunity against RSV challenge was shown in Rous sarcoma regressor, line CB (B12/B12). Immune cells from regressors of v-src DNA-induced tumors can protect syngeneic hosts from the development of tumor after challenge with both v-src DNA and RSV. Suppression of RSV-induced tumor cell growth in vitro was also achieved by the use of cocultivation with spleen cells from chickens in which v-src DNA-induced tumors had regressed. This in vitro sarcoma-specific response was Mhc(B)-restricted. Chickens of the congenic Rous sarcoma progressor line CC (B4/B4) are sometimes able to regress v-src DNA-induced tumors, but immune cells can only slow the growth of v-src DNA-induced tumors in syngeneic hosts. This suggests that the primary reason for the susceptibility of CC chickens is a weak v-src-specific immune response. Furthermore, some of the v-src DNA-induced tumors were transplantable across the Mhc(B) barrier. The growth of tumor allografts was able to be facilitated when immunological tolerance to the B-F/L region antigens (class I and class II) had been established. This demonstrated that a high tumorigenicity of the transplantable tumor was not due to the lack of Mhc(B) antigens on tumor cells.

Animals↗
PubMed1994

Immunohistochemical analysis of cells infiltrating Rous sarcoma virus-induced tumors in chickens.

The aim of our experiments was the analysis of peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) in chicken inbred congenic lines, CB line with regressing and CC line with progressing RSV-induced sarcomas. For serological analysis, monoclonal antibodies to CD4, CD8, TCR1, TCR2, MHC class I and class II antigens were used. Significant differences determined by flow cytometry in CD4+ and CD8+ populations of PBL between CB chickens with tumors in progressive phase and CC chickens were not confirmed by means of TIL analysis. TIL were analysed either in suspension prepared from tumors by means of flow cytometry or on cryostat section of tumors. But using the histochemical method we observed more non-specific esterase positive cells in cryostat sections from CB than CC tumors. The role of macrophages in the regression of RSV-induced tumors in CB chickens has to be further analysed.

Animals↗
PubMed1992

Frequency of chicken CD4+ and CD8+ cells. Genetic control and effect of Rous sarcoma virus infection.

In chickens from congenic inbred lines CB and CC that differ only in the major histocompatibility complex (MHC), we observed significantly different percentages of CD4+ and CD8+ cells in peripheral blood lymphocytes (PBL) and spleen. Positive cells were detected by indirect immunofluorescence test as analysed by flow cytometry. In both PBL and spleen cell suspensions, the number of CD4+ cells was significantly higher in CB than in CC chickens, whereas in CC birds there was a higher percentage of CD8+ cells than in CB. These statistically significant differences were under the MHC control. We found no statistically significant influence of regressions or progression of Rous sarcoma virus-induced tumours on the percentage of peripheral T cells and on the interleukin-2 production in vitro.

Animals↗
PubMed1992

Target organ susceptibility and autoantibody production in an animal model of spontaneous autoimmune thyroiditis.

F1-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe thyroiditis. About 50% of these crosses show circulating autoantibodies to thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated, suggesting that the target organ is not susceptible to autoimmune attack. In the present study we show that despite this mild infiltration TgAAb are only synthesized by lymphoid cells within the thyroid gland. Furthermore, we demonstrate that immunization with chicken thyroglobulin (Tg) in complete Freund's adjuvant causes severe experimental autoimmune thyroiditis (EAT) in F1(OSxCB) hybrids.

Animals↗
PubMed1992

Biology of the chicken MHC (B complex).

The major histocompatibility complex (MHC) of chicken is the B complex, originally described as a blood group system. Its three classes of cell membrane antigens have been clearly defined by serological, histogenetic, biochemical, and molecular biological methods. Two of these classes are homologous to classes I and II of mammals (B-F and B-L respectively), while the third--B-G antigen--has not so far been detected in mammals. The possible role of this antigen is discussed. The genes of the MHC play important roles in the regulation of immune response, disease resistance, and regression of Rous sarcomas.

Animals↗
PubMed1991

Chicken major histocompatibility complex congenic lines differ in the percentages of lymphocytes bearing CD4 and CD8 antigens.

In the experiments to be described two congenic inbred lines CB and CC and two recombinant lines CB.R1 and CC.R1 were used. All four lines differ only in regard to the major histocompatibility complex (MHC). To determine the percentage distributions of the two cell subsets in peripheral blood lymphocytes (PBL) in these lines, monoclonal antibodies to these two antigens were used. By FACScan there were more CD4+PBL in CB and CB.R1 lines (share B-F/B-L region, controlling class I/class II antigens with line CB) than CC and CC.R1, while the reverse was true with CD8+ subsets. There were more CD8+ PBL in the CC and CC.R1 lines and less in CB and CB.R1 lines. The ratio of CD4+ to CD8+ in CB chickens was 3.4 +/- 0.2 and in CC chickens 1.6 +/- 0.1.

Animals↗
PubMed1990

Intrathymic nurse cell lymphocytes can induce a specific graft-versus-host reaction.

Single chicken thymic nurse cells (TNC) placed onto the chorionallantoic membrane (CAM), showed that intra-TNC lymphocytes (TNC-L) possess a strong graft-versus-host reactivity (GVHR) in allogeneic MHC combinations. This reaction shows the morphological, phenotypic, and functional characteristics of a classical GVH reaction (GVHR). The induction of a GVHR was significantly higher for TNC-L as compared with thymocytes or peripheral blood lymphocytes (PBL). The specificity of the GVHR was shown by serial transfer experiments onto appropriate allogeneic and syngeneic secondary embryonic hosts. In immunofluorescence analyses with monoclonal antibodies (mAb) to the chicken alpha/beta and gamma/delta T cell receptors (TCR) and the CD3, CD4, and CD8 equivalents, an enrichment of CD3+/CD4+/CD8- and CD3+/CD-4-/CD8+, TCR-alpha/beta + and TCR- gamma/delta + cells was observed inside TNC as compared with extra-TNC thymocytes. A large proportion of CD4+ and/or CD8+ TCR- gamma/delta + cells were demonstrated inside TNC. A minor population among TCR- gamma/delta extra-TNC thymocytes also expressed CD4 and/or CD8 molecules. Based on functional tests and double staining experiments, we propose that CD4+/CD8+ thymocytes enter the TNC where they may undergo positive selection for MHC restriction and further differentiation to CD4 or CD8 single-positive cells. Taken together these data support the concept that TNC contribute a specialized thymic microenvironment for T cell differentiation and maturation.

Allantois↗
PubMed1989

Typing of MHC haplotypes in OS chicken by means of RFLP analysis.

For the analysis of the genetic background of autoimmune thyroiditis we used the Obese strain (OS) chicken model which develops a SAT. Practically all animals from this strain show severe lymphoid infiltration of the thyroid gland and circulating autoantibodies against thyroglobulin (Tg-AAb) within a few weeks after hatching. Of the 3 MHC haplotypes (B5, B13, B15) present in the OS, B13 was mostly associated with severe thyroid infiltration. Haplotypes B5 and B15 were associated both with severe, as well as with mild infiltration. To clarify these controversial results published by different groups and to further assess the role of the MHC in the development of SAT, we selected by appropriate breeding sublines with high and low levels of Tg-AAb. With the help of serological methods and GvH assays we were not able to find additional differences in the MHC antigens of that line. Therefore, for further characterization of these haplotypes, RFLP analysis was applied in the present study. Southern blots were done with restriction enzyme digests of erythrocyte DNA hybridized with a chicken cDNA probe (code-p234) for MHC class II antigens. The Southern blots with BamH-I digests showed at least 5 bands, four of which were polymorphic. Four RFLP patterns emerged, two of which were observed within chickens with the B15 haplotype. The confirmation of this RFLP heterogeneity within serologically identical haplotypes requires additional analysis.

Animals↗
PubMed1988

Genetic analysis of extrathyroidal features of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis.

The Obese strain (OS) of chickens, which is afflicted with Hashimoto-like spontaneous autoimmune thyroiditis (SAT), displays elevated T cell proliferation, interleukin (IL)2 production and IL2 receptor expression upon mitogen stimulation, and defects in the neuroendocrine control of the immune system including elevated corticosteroid-binding globulin (CBG) and a deficient increase of serum corticosterone (CN) upon cytokine injection. Recently this strain has further been shown to harbor retrovirus-related sequences (endogenous virus no. 22, ev22) absent in healthy control strains. To determine the number of genes responsible for SAT-associated immunodysregulation and to unravel possible ev22 associations, we analyzed the above immune and endocrine parameters in F1 hybrids and backcrosses of the autoimmune OS B15B15 with healthy inbred CB B12B12 chickens. OS-like T cell hyperproliferation and IL2 hypersecretion in response to both concanavalin A and phytohemagglutinin were transmitted as autosomal dominant traits and co-segregated in backcross animals. In vivo hyporesponse of the OS to the corticosterone-inducing effect of cytokine preparations was inherited dominantly and the elevated CBG serum levels recessively. None of these traits appeared to be major histocompatibility complex (MHC) linked. However, while T cell abnormalities and elevated CBG serum levels were not associated with the autosomal ev22 locus, in vivo hyporesponsiveness to glucocortocoid-inducing cytokines co-segregated with this OS-specific provirus. These results add to the concept of SAT as a polyetiological and plurigenetic disease and do not support our previous hypothesis that T cell hyperreactivity and immunoendocrine dysfunction might be functionally related.

Animals↗
PubMed1988

Attempt to detect recombination between B-F and B-L genes within the chicken B complex by serological typing, in vitro MLR, and RFLP analyses.

In search for recombinants within the chicken major histocompatibility B complex, 1155 animals from crosses between the congenic lines CB (B12) and CC (B4) were tested with alloantibodies and monoclonal antibodies for the B-F (class I), B-L (class II), and B-G (class IV) antigens and by mixed lymphocyte reaction. The absence of detectable recombination was confirmed by restriction fragment length polymorphism analysis with B-L beta and B-F probes. Together with previous reports, this indicates that the distance between the B-F and B-L loci is below 0.01 centimorgan.

Animals↗
PubMed1988

Chicken-activated-T-lymphocyte-antigen (CATLA) recognized by monoclonal antibody INN-CH 16 represents the IL-2 receptor.

Monoclonal antibody INN-CH 16 recognizes a surface determinant exclusively present on activated chicken T lymphocytes. The present experiments suggest that this chicken activated T lymphocyte antigen (CATLA) represents the chicken IL-2 receptor or an associated structure, as (i) the kinetics of CATLA expression during T cell activation are analogous to those described for the mammalian receptor for IL-2, (ii) the IL-2 dependent proliferation of mitogen prestimulated chicken lymphocytes is competitively inhibited by INN-CH 16, and (iii) pretreatment of T lymphoblasts with INN-CH 16 drastically reduces their capacity to absorb IL-2 activity from supernatants of mitogen activated chicken lymphocytes.

Animals↗