Characteristics and functions of CD4-, CD8- T cells in normal and autoimmune mice.
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Animals↗
Biomedical subjects
W C Gause
Publications and source records attributed to W C Gause.
Subpopulations of CD4-, CD8- thymocytes.
A population of highly purified CD4-,CD8- thymocytes was analyzed by both flow microfluorometry and in situ hybridization in an attempt to further elucidate thymocyte subpopulations. The double-negative cells had a marked increase in expression of the c-myb and T cell gamma genes relative to unseparated thymocytes. Approximately 27% were Ly-24+, 8% Ly-6C+ and 6% 6B2+. All of the Ly-6C+ cells were also Ly-24+. A small population (6%) of the CD4-,CD8- thymocytes had surface expression of the T cell receptor for antigen (F23.1); all were bright Ly-1+ and half were Ly-24+. These studies demonstrate that there are further subdivisions of the CD4-, CD8- thymocytes based upon cell surface expression of markers previously found on bone marrow cells and their non-T cell progeny. Studies are in progress to determine whether these represent different stages of activation-maturation or different lineages of cells.
Animals↗
Detection of a macrophage population in the thyroids of obese strain chickens using monoclonal antibodies.
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Age Factors↗
Genetic and molecular genetic studies of murine and human lupus.
Mice and humans with systemic lupus erythematosus (SLE) have been studied with regard to cellular, genetic and molecular genetic abnormalities. B cell hyperactivity and autoantibody production are the hallmarks of this illness. In humans with SLE, there is increased stem cell, B cell precursor and B cell proliferation. The same is true of NZB mice. In lpr/lpr and gld/gld mice, marked expansion of a subpopulation of T cells allows extrathymic terminal T cell maturation and secondary B cell hyperactivity. Androgens suppress these processes and polyclonal immune activators accelerate them. Three types of genes are identified: inducing genes, accelerating genes and background genes. These give rise to abnormal expression of various cellular oncogenes, T cell receptor genes and immunoglobulin genes. The data suggest that abnormal immune regulation plays a critical role in the development of SLE, with polyclonal B cell activation being common to both mice and humans with SLE. Different genetic and cellular abnormalities underlie the ultimate syndrome, the common denominator, generalized autoimmunity, that we call SLE.
Animals↗
Effect of testosterone treatments for varying periods on autoimmune development and on specific infiltrating leukocyte populations in the thyroid gland of obese strain chickens.
Spontaneous autoimmune thyroiditis (SAT) is detectable by 2 weeks of age in the obese (OS) strain of chicken, and by 6 weeks virtually all of these animals have severe lymphoid infiltration of the thyroid. During the interval from hatching to 6 weeks of age, testosterone implants were administered for varying periods. All treatment groups were terminated at 6 weeks. Testosterone administered shortly after hatching increased thymus weight, depressed bursa weight, and reduced the severity of SAT, as measured by lymphoid infiltration of the thyroid and circulating thyroglobulin autoantibody concentrations. Birds supplemented with testosterone at later intervals exhibited depressed bursa and thymus weight; however, the severity of SAT was not affected. In a second experiment, the treated group was administered testosterone for the first 2 weeks after hatching. Thyroids were histologically examined at 2 and 6 weeks using a panel of five monoclonal antibodies (anti-Ia, anti-IgM, anti-IgG, anti-T cell, and antithymocyte). Compared with untreated controls, testosterone treatment reduced the frequency of Ia+ cells, T cells, and IgG+ cells in the thyroid. This treatment did not affect the frequency of IgM+ cells, and perhaps slightly increased the frequency of thymocytes. These results suggest that testosterone's suppressive effects are associated with changes in thymic development and effector T-cell and regulator T-cell activity.
Age Factors↗
Effects of testosterone on the development of autoimmune thyroiditis in two strains of chicken.
The effect of testosterone on organ-specific spontaneous autoimmune thyroiditis (SAT) was examined in two strains of chicken: the Obese (OS) strain, which develops SAT at several weeks of age and the control Special C (Sp. C) strain. Both were originally selected from the C strain and are homozygous for the B13 major histocompatibility haplotype. Testes development and testosterone levels in the OS strain were considerably less than those found in comparably aged birds of the Sp. C strain. Testosterone supplementation of the OS strain significantly decreased thyroid infiltration by lymphocytes while castration of the Sp. C strain significantly enhanced infiltration. These results suggest that testosterone reduces SAT and that the hormonal constitution in both strains of chicken affect the frequency of occurrence and severity of this disorder.
Age Factors↗
Differential effects of thyroxine on immune development and autoimmune thyroiditis in the obese strain chicken.
The effects of dietary thyroxine (T4) supplementation for specific periods on the early development of the primary lymphoid organs and spontaneous autoimmune thyroiditis (SAT) was examined in the Obese (OS) strain of chicken. Effects of the treatments on concentrations of serum growth hormone (GH) and testosterone were also determined. All treatment groups were examined at 6 weeks. T4 supplementation did not affect serum testosterone or GH concentrations. However T4 given for the first three weeks resulted in significantly increased bursa weights, no change in thymic weights, significantly decreased lymphoid infiltration of the thyroid and reduced thyroglobulin autoantibody levels (TgAAb). T4 supplementation for the full six weeks resulted in no change in bursal weight, significantly increased thymic weight, significantly decreased lymphoid infiltration of the thyroid, and reduced TgAAb. These results suggest that the effects of T4 supplementation on SAT and immune development are dependent on the interval during which it is administered and that testosterone and GH probably do not mediate these effects.
Animals↗
Autoanti-thyroglobulin production in obese chickens: influence of age and sex as measured by ELISA.
The kinetics of serum autoantibody production against thyroglobulin (Tg) was examined in two strains of chicken using an enzyme-linked immunosorbant assay (ELISA). Both strains are homozygous for the B13 haplotype. The OS strain develops spontaneous autoimmune thyroiditis at several weeks of age while the Sp. C strain, which serves as the control for the OS strain, has virtually undetectable autoantibody levels as determined by hemagglutination assay (HA). Serum autoantibody levels in both strains were monitored bi-weekly from 6 through 14 weeks of age post-hatching, using both the ELISA and HA techniques. With the more sensitive ELISA, absolute serum autoantibody concentrations were determined and both the Sp. C and OS strains were found to have readily detectable serum autoantibodies against Tg; however, the OS did have significantly higher autoantibody levels than the Sp. C strain. In the latter strain, autoantibodies increased significantly with age while the pattern was somewhat reversed in the OS strain. The ELISA revealed that the decline of Tg autoantibodies with age in the OS strain was restricted primarily to males, with females maintaining constant levels of autoantibodies. In contrast, the HA detected only the differences in autoantibody levels between the OS and Sp. C strains.
Aging↗
Enhanced growth and immune development in dwarf chickens treated with mammalian growth hormone and thyroxine.
The effects of growth hormone and/or thyroxine treatments on antibody production, primary lymphoid organ development, and general body growth were examined in two dwarf strains (sex-linked dwarf--SLD, and autosomal dwarf--ADW) and in a normal-growing strain (K) of White Leghorn chickens. One-day-old male chicks were assigned to experimental groups and were treated either with thyroxine (T4) feed supplements or daily mammalian growth hormone (GH) injections or a combination of these treatments (T4/GH). Within the SLD strain, GH treatments resulted in a significant enhancement (P less than 0.005) of humoral immune responsiveness and bursal growth while T4 treatments significantly (P less than 0.05) stimulated thymic growth. Overall growth in the SLD was also stimulated by T4 treatments. GH and/or T4 treatments had no specific effects on primary lymphoid organ growth in the ADW strain but either treatment separately resulted in a significant (P less than 0.05) increase in overall body size. None of the treatments significantly (P greater than 0.05) affected any of these parameters in the K-strain controls. Supplementation with T4 significantly elevated serum T4 levels within all strains. There were, however, no significant differences in the serum levels of T4 between strains within any of the treatment groups. Serum triiodothyronine (T3) levels were significantly lower in all treatment groups of the SLD as compared to the K-strain control. ADW serum T3 levels were significantly lower than the K-strain only in the T4-treated group. No differences (P greater than 0.05) were found between the dwarf and control strains in endogeneous GH levels, although mammalian GH treatments did produce significant changes in serum T3 and T4 levels within the K-strain. These results provide evidence that hormonal manipulations can significantly affect body growth, primary lymphoid organ development, and immune function in the dwarf strains studied and suggest these strains may be useful models for future studies on hormonal interactions and immune function.
Animals↗