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R K Jordan

Publications and source records attributed to R K Jordan.

At least 19 recordsLinked to original sources
PubMed1992

T-cell tolerance induced in nude mice grafted with thymic epithelium.

This study investigated the ability of foetal thymic epithelium prepared by 24 degrees culture (24 degrees-TE) or treatment with deoxyguanosine (dGuo-TE), to induce tolerance in nude mice. Thymic chimeras were constructed in which the thymic epithelium differed from the host at both major histocompatibility complex (MHC) antigens and multiple minor histocompatibility antigens (mHa), or at mHa only. Peripheral CTL from nude mice receiving dGuo-TE disparate for mHa, or both MHC antigens and mHa, were uniformly tolerant of thymic mHa. CTL from nude mice grafted with 24 degrees-TE or dGuo-TE were tolerant of host MHC antigens, but the two treatments differed in the efficiency with which they induced tolerance to thymic MHC antigens. CTL responses specific for thymic MHC antigens could be generated in vitro from dGuo-TE grafted mice but not from those receiving 24 degrees-TE. The addition of concanavalin A (Con A) supernatant had no effect on the CTL tolerance observed in 24 degrees-TE grafted mice, suggesting that the lack of CTL responses was not due to tolerance in MHC class II restricted 'helper' cells. However, CTL responses against the thymic MHC antigens of dGuo-TE grafted mice displayed high sensitivity to blocking by anti-CD8 antibodies, indicating that these CTL were of low affinity. These results suggest that 24 degrees-TE induces tolerance in most thymic MHC-specific CTL precursors, whereas dGuo-TE induces tolerance only in CTL with high affinity for thymic MHC antigens. Therefore, 24 degrees-TE and dGuo-TE are both capable of inducing CTL tolerance, consistent with the previously reported acceptance of thymic donor-type skin grafts by nude recipients of dGuo-TE treatment. We conclude that MHC class I molecules on thymic epithelium play a role in negative selection of the developing T-cell repertoire.

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PubMed1990

Thyroid peroxidase and the induction of autoimmune thyroid disease.

Animal models of autoimmune thyroid disease are associated with thyroglobulin (Tg) as autoantigen whereas in man the autoimmune response to microsomal antigen/thyroid peroxidase (TPO) appears to play a major role in thyroiditis. Consequently, we have compared the ability of TPO and Tg to induce thyroid autoantibodies and thyroid damage in mice known to be susceptible (CBA/J) or resistant (BALB/c) to thyroiditis induced using murine Tg. Groups of three to five mice were immunized twice using Freund's complete adjuvant with 80-100 micrograms highly purified porcine (p) TPO, pTg, rat (r) Tg, human Tg, bovine serum albumin (BSA) or BSA + 0.2 micrograms pTg (the level of Tg contamination of TPO). Four weeks after immunization with TPO, plasma from CBA/J (but not BALB/c) mice contained IgG class antibodies which bound to TPO-coated tubes in the presence or absence of excess Tg (and could therefore be clearly distinguished from Tg antibodies) but there was no evidence of thyroiditis in either strain of mice. In contrast, in CBA/J mice immunized with rTg and, to a lesser extent in mice that had received pTg, thyroid tissue was infiltrated with lymphoid cells and/or neutrophils and antibodies to pTg (but not pTPO) were present. Our observations demonstrate that induction of TPO antibody alone is insufficient to lead to thyroiditis in CBA/J mice. Further, these studies emphasize the complex interactions between MHC and different thyroid antigens in the processes leading to thyroid destruction.

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PubMed1990

IgG antibody and delayed-type hypersensitivity responses in nude mice grafted with thymic epithelium.

This study compared the ability of foetal thymic epithelium depleted of lymphocytes and dendritic cells, by low temperature or deoxyguanosine (dGuo) treatment in organ culture, to reconstitute T-cell function in nude mice. It is shown that renal capsule grafts of either type could promote the development of functional T lymphocytes in the periphery, as judged by in vivo assays. Both syngeneic and allogeneic thymic epithelium endowed nude mice with the capacity to mount IgG antibody and delayed-type hypersensitivity (DTH) responses to the T-dependent antigen ovalbumin (OVA). Functional reconstitution was accompanied by the appearance of Thy-1-bearing cells in the spleens of thymic grafted nude mice. The results from allogeneically grafted recipients show that a substantial population of peripheral T cells was present that collaborated with B cells and other antigen-presenting cells (APC) which do not express major histocompatibility complex (MHC) molecules of the thymus donor haplotype.

Animals↗
PubMed1990

IL-3 and IL-4 affect thymocyte differentiation in organ culture.

The ability of lymphokines to affect the development and differentiation of mouse thymocytes in vitro was evaluated in a carefully controlled 3-day organ culture system. Concanavalin A (Con A)-induced supernatant (SN) from the T-cell clone D10.G4, which contains high concentrations of interleukin-3 (IL-3), IL-4 and IL-5, but lacks IL-1, IL-2 and interferon (IFN), markedly increased the proportion of CD4+CD8- cells, and decreased the proportion of CD4+CD8+ cells. These effects were unaffected by dialysing the SN, showing them to be caused by macromolecular factors. Highly purified recombinant IL-3 and IL-4 could exert similar effects, rIL-3 and rIL-4 both increasing the proportion of CD4+CD8- cells, and rIL4 in addition reducing the proportion of CD4+CD8+ cells. In conjunction with the findings of other investigators, these results indicate that at least four lymphokines (IL-1, IL-2, IL-3 and IL-4) can control T-cell development in the thymus.

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PubMed1987

Delayed type hypersensitivity responses to the Qa-Tla region of the mouse major histocompatibility complex.

We have elicited a small but significant delayed-type hypersensitivity response against the Qa-Tla region of H-2 following immunisation of C57BL/6 mice with cells from the congenic strain C57BL/6.Tlaa. Optimal responses were detected 14 days after immunisation with 10-40 X 10(6) cells. The significance of delayed type hypersensitivity to Qa-Tla is discussed in relation to the genetic loci which map to this region.

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PubMed1985

Thymic epithelium. I. Lymphoid-free organ cultures grafted in syngeneic intact mice.

Low temperature organ culture of 14 day gestational age mouse thymic lobes leads to the development of a lymphoid-free epithelial matrix. Morphologically, these explants exhibit two distinct epithelial components, which may be indicative of the dual embryologic origin (ectodermal/endodermal) of the thymic epithelium. When such explants are grafted into syngeneic intact recipients, the compound matrix is repopulated by lymphohematopoietic precursors that give rise to an intragraft lymphocyte population. The graft shows additional morphologic development parallel to normal thymus ontogeny. Studies in congenic mice when using the TIa alloantigen as a marker of derivation demonstrate the host origin of these lymphocytes. Cytotoxic assays for the presence of cell surface Thy-1.2, TIa, Lyt-1.2, and Lyt-2.2 reveal that graft lymphocytes express a phenotypic profile and developmental progression that is typical of normal thymocytes. Furthermore, mitogen and mixed leukocyte culture assays show that intragraft lymphopoiesis leads to the generation of a mature population. In addition to the lymphocytes, host-derived Ia+ adherent cells can also be isolated from these thymic epithelial grafts. We conclude that low temperature organ culture-derived thymic epithelium appears to retain those properties of the thymic microenvironment that permit lymphohematopoietic colonization and support thymocyte differentiation.

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PubMed1977

Organ culture studies of nude mouse thymus.

There is evidence that peripheral lymphoid organs of nude mice, born from homozygous matings, contain a small proportion of theta-positive lymphocytes indicating that nude mice may not be totally devoid of T cell function. It has been suggested that such lymphocytes may develop within the dysplastic nude thymus itself. While this suggestion receives no support from morphological studies, it has been claimed that on explanation to organ culture the developing nude thymus becomes lymphoid. In this present study we confirm the presence of theta-positive lymphocytes in peripheral lymphoid tissues of homozygous nude mice born of nude parents. However, when we have organ-cultured nude thymus, explained from homozygous nude embryos at days 13, 14, 16 and 18 of gestation, we have found no histological sign of lymphopoiesis nor have we detected any theta-positive cells in such cultured material. On the contrary, the nude thymus in vitro develops into the polycystic structure characteristic of the adult nude thymus. We conclude that the small number of theta-positive cells present in the periphery result from extrathymic differentiation.

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PubMed1976

Development of sheep thymus in relation to in utero thymectomy experiments.

The developing thymus of sheep embryos has been examined from 20 days of gestation onwards. The initial relationships of the thymus to the parathyroid III and the pericardium are maintained so that the thymus develops as an extensive and complex structure consisting of paired cords of tissues on either side of the neck continuous with a single, fused structure in the anterior mediastinum. Histological examination of the developing thymus revealed that thymic lymphopoiesis commences at 36 days of gestation (term = 150 days). The results indicate that conclusions drawn from sheep thymectomy, usually performed after 60 days of gestation, must be interpreted with caution.

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PubMed1975

An electron microscopic study of the histogenesis of the parathyroid gland in the sheep.

Definitive chief cells, characterized by the presence of specific secretory granules and typical membrane configurations, were present in the developing parathyroid glands of sheep embryos from 26 days of gestation (term = 150 days). During earlier stages of gestation developing chief cells contained lysosomal systems which appeared to be concerned with the autophagy of retained secretion product. The EM evidence suggests that physiologic release of the hormone does not occur until at least 30 days of gestation, which correlates well with the experimentally established time of onset of functional capacity in the parathyroid gland in the sheep. 'Bark cells' were found in the parathyroid primordia of embryos between 20 and 27 days of gestation. The significance of these "dark cells" is discussed with respect to glutaraldehyde fixation and to their possible relationship to chief cells.

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