Joseph H. Kite

Hereditary Autoimmune Thyroiditis in the Fowl

In the Cornell C strain of White Leghorn chickens, thyroiditis appeared spontaneously. It was characterized by phenotypic changes due to a decrease of thyroxine, histological damage to the thyroid gland, and the presence in the seruim of antibodies to thyroglobulin. Susceptibility to the disease is genetically inherited. Hormonal bursectomy (androgen given to the embryo) suppresses the development of thyroiditis.

Relation between the Major Histocompatibility (B) Locus and Autoimmune Thyroiditis in Obese Chickens

Obese strain chickens develop circulating autoantibodies to thyroglobulin and lymphocytic infiltration of their thyroids during aging. Two alleles, B1 and B4, are found with high gene frequency at the major histocompatibility (B) locus. Greater pathology and higher antibody titers are observed in B1B1 and B1B4 birds than in their B4B4 siblings.

Studies on experimental thyroiditis.

The increasing attention directed to the role of autoimmunity in the pathogenesis of various diseases requires tha t efforts be intensified to elucidate the biological mechanisms underlying the phenomenon. For this purpose, studies of human disease are profitably coupled with investigations using experimental animals, where the immunological and pathological consequences of autosensitization can be observed under controlled conditions. Because of its resemblance to human chronic thyroiditis, experimental thyroiditis represents a particularly significant model. This autoimmune disease can be produced in several animal species including the rabbit, guinea pig, dog, rat, and mouse by injection of autologous, homologous or even heterologous thyroid protein, usually with Freund adjuvant. I t is characterized by formation of circulating autoantibodies and of delayed hypersensitivity to thyroglobulin, and by development of inflammatory changes in the animals own thyroid gland. Major problems exist in our understanding of the induction of this disease, its transfer from one animal to another, and the mechanisms actually responsible for cellular damage. The purpose of this paper is to survey briefly some current investigations underway in our laboratory on these topics.

Immunogenetic Detection Of b Locus Genotypes In Chickens With Autoimmune Thyroiditis

An effective approach is described for determining the B locus genotypes in a strain of outbred chickens. Matings were established within the strains studied to produce pedigreed offspring. A portion of the embryos produced was injected with blood from the sire or dam and their spleens were observed for graft-versus-host response. In other cases chicks were hatched and grafted with skin or wattle tissue from both their parents and two full sibs. Subsequently, grafted chicks were immunized with parental erythrocytes known to be incompatible for one B allele based on the results of the skin grafts and graft-versus-host studies. Eventually, antisera specific for B locus antigens were obtained. In Obese strain (OS) birds that spontaneously develop autoimmune thyroiditis two B alleles, B1 and B1, were identified with approximately equal gene frequency. A third allele, B3, was identified and observed only rarely (r = 0.04). Only one of the frequent alleles of OS chickens, B1, was identified in the parent White Leghorn Cornell C strain (CS) population from which OS chickens were selected. The frequency of B1 was similar in both strains. The B3 allele and another allele, B2, were present in moderate frequency in CS. Matings of B1B4 OS heterozygotes resulted in the segregation of offspring into the expected genotype ratio of 1 B1B1:2 B1B4:1 B4B4, verifying that the sera were specific for antigens determined by alleles of one locus. Several antisera specific for B locus antigens produced in other lines of chickens were used to test crythrocytes of OS and CS birds having different B genotypes. The agglutination results obtained with these sera substantiated the specificity of the antisera for B locus antigens.

Virological investigations of chickens with spontaneous autoimmune thyroiditis. I. Isolation and transmission studies.

The autoimmune nature of spontaneous chronic thyroiditis in the Obese Strain (OS) of White Leghorn chickens has been reported previously (2). Additional documentation of these findings has included studies on the nature of the antibodies (8), the spontaneous development of the disease (3), and the consequences of bursectomy (6) and thymectomy (7). The potential usefulness of this model in studies of autoimmune processes has been emphasized. An important aspect of the problem concerns the possible role that a virus may play in the pathogenesis of this disease. In the studies reported in this and a following paper (9), no evidence was obtained of viral infection in spontaneous autoimmune thyroiditis. Four strains of chickens were used. The OS chickens were derived from the Cornell C-strain during 1955-1958 (1) and bred as a closed flock for more than eight generations (The historical data on the OS and C-strains were supplied by Dr. R. K. Cole, Cornell

Effect of mycoplasma infection on esterase activity of human FL amnion and WI-38 cells.

Summary Lateral cerebral ventricular administration of sodium salicylate (0.25-1.00 mg) and acetaminophen (0.50-1.00 mg) significantly inhibited production of fever by LP injected iv in the cat. Acetaminophen also caused mild but significant hypothermia in the absence of fever. The ability of these antipyretics to antagonize fever produced by LP, and by agents such as bacterial pyrogens which release LP, is most likely due primarily to a central action to inhibit the effect of LP rather than to a peripheral action to alter LP release from leukocytes or to inhibit entry of LP into the central nervous system. Note added in proof. Since this paper was submitted for publication, evidence for a central antipyretic action of sodium acetylsalicylate against LP-induced fever in the monkey has been reported by Chai, C. Y., Lin, M. T., Chen, H. I., and Wang, S. C., Neuropharmacology 10, 715 (1971). The authors wish to thank Barbara Coldwell for her assistance with some of these experiments.

Loss of organ specific characteristics of hog thyroid cells during growth in vitro.

Summary Normal hog thyroid glands were treated with enzyme and the dispersed cells cultured in vitro. Radioactive iodide (I125) was added to the growth medium so that the duration of synthesis of thyroglobulin, MIT, DIT, T3, and T4 could be measured. Thyroglobulin production was measured by radio-immunoelectrophoresis and tanned cell hemagglutination inhibition tests. The iodinated amino acids were analyzed by hydrolyzing cell sonicates and separating the iodoamino-acids by thin-layer chromatography. Radioactivity of each amino acid was detected by direct counting in a well scintillation counter and by observation of a radioautograph prepared from a duplicate chromatography plate. Thyroglobulin was synthesized during the first 3 days of in vitro growth. Radioactively labeled T3 and T4 were detected during this same time period. The synthesis of MIT and DIT continued for at least 2 additional days. Serum albumin containing I125 was detected by radioimmunoelectrophoresis during the first 7 days of growth. Hog kidney cells when tested in an identical manner did not iodinate proteins or amino acids.

TISSUE CULTURE STUDIES OF CILIATED RESPIRATORY EPITHELIUM.

Abstract Several methods are described for obtaining and growing ciliated respiratory epithelium in tissue culture. The addition of specific antigens to mucosa obtained from allergic patients and sensitized animals did not cause any detectable alterations in the frequency or coordination of the ciliary beat. Patients with chronic bronchitis and intrinsic (nonallergic) bronchial asthma generally had poor ciliary activity.