Biomedical subjects
L D Bacon
Publications and source records attributed to L D Bacon.
Skin-graft histocompatibility within Regional Poultry Research Laboratory inbred chicken lines.
Skin grafts were exchanged between specific-pathogen-free chicks within the Regional Poultry Research Laboratory (RPRL) inbred lines that are characterized for retrovirus susceptibility and immunogenetic traits. Lines 61 and 63 were histocompatible whereas lines 15I4 and 15I5 were nearly histocompatible. The RPRL Line 7(2) is only histocompatible within families at present, and line 100 has considerable heterogeneity for minor histoantigens. Reaseheath Line C (RH-C) has been established at the RPRL and its histocompatible. Numerous males in lines 6(1), 6(3), 15I4, and RH-C are able to reject female grafts containing the female-specific histoantigen. Two Ea-B alleles in 15I4 previously detected by blood-typing determined rapid skin graft rejection.
Allograft and mixed lymphocyte response studies in 6(3) X 15(1) F6 chickens.
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Tests of association of lymphocyte alloantigen genotypes with resistance to viral oncogenesis in chickens. 1. Marek's disease in F7 progeny derived from 6(3) X 15(1) crosses.
Marek's disease (MD)-susceptible progeny of the B5B5 genotype from the F7 generation derived from crosses of Regional Poultry Research Laboratory inbred lines 6(3) and 15(1) were tested for variation in MD resistance associated with the T lymphocyte antigen loci Ly-4 and Th-1. The four double homozygous genotypic classes of Ly-4 and Th-1 were tested in a 2 X 2 design. The Ly-4bb/Th-1aa chickens were significantly more resistant to MD oncogenesis than the other three genotypes. Thus, resistance within B5B5 genotypes appears to be associated with genetic interaction between two T cell antigen loci, which are not linked with the B complex.
Genetic influences on spontaneous autoimmune thyroiditis in (CS X OS)F2 chickens.
Genetic effects on spontaneous autoimmune thyroiditis in chickens were assessed by measuring phenotypic symptoms, the titer of circulating antibody to thyroglobulin, and the pathological change in the thyroids of young chicks. One or more loci within the B complex (the major histocompatibility complex of the chicken) are responsible for the expression of autoimmunity, and evidence is provided for an interaction of the B haplotype with genes at other loci. The influence of the B complex component on genetic susceptibility is more visible in animals with limited susceptibility at other loci and becomes indistinguishable as the frequency of other genes determining thyroid autoimmunity increases.
B-haplotype influence on Marek's disease, Rous sarcoma, and lymphoid leukosis virus-induced tumors in chickens.
Experiments were conducted to establish whether B-haplotype genes that determine resistance to RSV-induced tumors would also influence resistance to Marek's disease and lymphoid leukosis. Matings of line 6(3) x 15(1) F3 or F4 breeders segregating for the Ea-B locus antigens that are markers for B2 and B5 haplotypes of the B major histocompatibility complex were made to produce B2B2, B2B5, and B5B5 chicks. The chicks were infected with a standard inoculum of one of the three tumor viruses in separate experiments. The B2 haplotype from 6(3) conveyed greater resistance to tumors induced by all three viruses than the B5 from 15(1) chickens. This finding suggests that some gene(s) in the B-haplotype may determine a general ability to resist tumor formation or cause tumor regression.
Influence of age on reactivity of 1-way mixed lymphocyte cultures in young chickens.
A reproducible 1-way mixed lymphocyte culture (MLC) assay was used to study the ontogeny of MLC in N, P, RPRL-72 and RPRL-63 strains of chickens. The chicks were progeny of specific-pathogen-free and lymphoid leukosis virus-free parents and grown in common isolators. When cells were from responder and stimulator chickens of the same age, the RPRL-72 chickens cells responded by 8 wk, whereas cells from chickens of the other 3 strains did not respond significantly until after 14 wk of age. In MLC with 6- and 32-wk-old RPRL-72 and N birds, the age of the responder was not crucial. However, young or old N birds responded extremely well to old 72 stimulator cells, whereas young 72 cells stimulated no, or minimal, response. Thus the age of the stimulator cell is vary important in chicken MLC and appears to depend upon the responder chicken strain.
Spontaneous autoimmune thyroiditis in chickens. I. Effects of bursal reconstitution.
Chicks from strains genetically susceptible or resistant to spontaneous autoimmune thyroiditis were neonatally treated with cyclophosphamide to induce lymphocytic depletion of the bursa of Fabricius. The subsequent bursal repopulation with B cells from donors matched at the major histocompatibility locus showed B cells to be intricately associated with the pathogenesis of spontaneous autoimmune thyroiditis, although they themselves did not carry the potential for initiation of the disease.
Influence of major histocompatibility haplotype on autoimmune disease varies in different inbred families of chickens.
Three partially inbred substrains of Obese strain chickens were studied for the spontaneous development of autoimmune thyroiditis. The influence of the major histocompatibility complex (B haplotype) was marked in one, less marked but still significant in a second, and barely detectable and transient in a third substrain. These differences in the effect of B haplotype may be due to the overriding action of genes other than those within the B haplotype.
Depression of vaccinal immunity to Marek's disease by infection with reticuloendotheliosis virus.
The effect of infection with low-virulence, tissue culture-propagated strains of reticuloendotheliosis virus (REV) on protective vaccinal immunity against Marek's disease (MD) lymphomas was investigated. Vaccinated chickens inoculated at hatching with greater than 10(4) focus-forming units of REV and challenged with MD virus were poorly protected against MD lesion development as indicated by protective indices of 53 to 79% for strain CS (P less than 0.05) and 42 to 49% for strain T (P less than 0.01) compared to 78 to 100% for REV-free controls. Furthermore, the response of blood lymphocytes to mitogen stimulation and the antibody response to sheep erythrocytes and Brucella abortus were less in REV-inoculated chickens than in controls. The REV-induced depression of immune responses was more severe in chickens infected with mildly pathogenic strain T than in chickens infected with the apathogenic strain CS and was generally transient with both virus strains. Little or no depression of immune responses was observed in chickens inoculated with less than 10(3) focus-forming units of REV. These studies extend knowledge on the immunodepressive ability of low-virulence REV strains and establish that infection with these viruses depresses certain parameters of MD vaccinal immunity, an important model for cellular immunity against virus-induced neoplasia in the chicken.
Fc receptor-bearing lymphoid cells in the chicken. I. Characterization of the Fc(IgG) receptor.
The receptor for FC(IgG) on chicken lymphoid cells was investigated by EA rosette techniques using sheep erythrocytes sensitized with a sub-agglutinating dose of anti-sheep erythrocyte (SRBC) chicken serum. Chicken lymphocytes did not form rosettes with SRBC coated with rabbit antibody, and human and mouse lymphocytes did not bind SRBC sensitized with chicken antibody. Only avian sera were effective in blocking the Fc receptor. Similarities between chicken and mammalian Fc receptors were demonstrated as both are pronase sensitive, trypsin resistant, and are distinct from surface immunoglobulin. Fc receptors were also distinguished from avian bursa- and thymus-specific antigens. Additional Fc receptor-bearing cells were revealed in bursa, spleen and bone marrow lymphocytes after neuraminidase treatment.
Fc receptor-bearing lymphoid cells in the chicken. II. Relative increase of Fc(IgG) receptor bearing cells in obese strain-chickens.
An EA rosette technique is used to study ontological development and organ distribution of Fc(IgG) receptor-bearing lymphoid cells in normal CS White Leghorn chickens, and in OS chickens with spontaneous autoimmune thyroiditis. During the embryonic period, no difference was seen between CS and OS in the tissue distribution of cells with Fc receptors. At the time of hatching and subsequently, the OS chickens possessed relatively more Fc receptor-bearing lymphoid cells than did CS chickens. The increase of Fc receptor-bearing lymphoid cells was most prominent among spleen cells. No difference in the affinity of Fc receptors between lymphocytes of the OS and CS chickens was demonstrated. The possible role of Fc receptor-carrying cells in the development of autoimmune thyroiditis is discussed.
Bursa-independent origin of Fc IgG receptor-bearing lymphocytes in chickens.
On the basis of performed studies the following observations indicate that there is a bursa-independent origin of lymphocytes with Fc IgG receptors: (a) the first appearance of Fc positive cells is in fetal liver and bone marrow, (b) a relative low percentage of Fc receptor cells, as compared to B cells, occurs in the bursa during the embryonic and post-hatching period, (c) a far lower percentage of Fc positive cells than B cells is found in the spleen, (d) a normal level of Fc positive cells occurs in bursectomized birds, (e) a majority of these cells do not possess thymic or bursa antigen or surface immunoglobulin.
Genetic and cellular control of spontaneous autoimmune thyroiditis in OS chickens.
B-locus genotypes have been defined in Obese strain (OS) chickens that spontaneously develop autoimmune thyroiditis (SAT), and in White Leghorn Cornell C strain (CS) chickens from which the OS was selected. The B-locus influences SAT, and some possible mechanisms are discussed. Thymic abnormalities in OS, as contrasted with CB birds, are also discussed and may play a role in SAT, as may an intrinsic defect in the thyroid gland itself.
Immunogenetic and ontogenetic studies of chickens with selective IgA deficiency and autoimmune thyroiditis.
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Abnormal response to minor histocompatibility antigens in Obese strain chickens.
Obese strain chickens, which spontaneously develop autoimmune thyroiditis, were tested for their ability to tolerate skin allografts. Several procedures known to prolong graft survival in normal strains were employed. These included the use of skin matched at the major histocompatibility locus, grafting on the day of hatching, thymectomy, and x-irradiation. A dramatic difference between the Obese and the normal Cornell strain (the strain from which Obese was derived) was detected when both were thymectomized and grafted at hatching. Under these conditions eight of 13 normal but only one of 16 Obese strain birds retained their grafts for 50 days. This suggests the presence of an abnormal thymus or thymus-derived suppressor T cells in Obese strain chickens.
Genetic determinants of thyroiditis in the OS chicken.
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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, B(1) and B(4), are found with high gene frequency at the major histocompatibility (B) locus. Greater pathology and higher antibody titers are observed in B(1)B(1) and B(1)B(4) birds than in their B(4)B(4) siblings.