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R D Hunziker

Publications and source records attributed to R D Hunziker.

11 recordsLinked to original sources
PubMed1999

Expression of the mutant thyroid hormone receptor PV in the pituitary of transgenic mice leads to weight reduction.

Resistance to thyroid hormone (RTH) is a genetic disease caused by mutations of the thyroid hormone receptor beta gene (TRbeta). One of the symptoms in some affected individuals is growth retardation. To understand the molecular basis of growth retardation in these patients with RTH, a transgenic mouse was prepared in which the expression of the TRbeta1 mutant PV was targeted to the pituitary using the promoter of the glycoprotein hormone alpha-subunit. The PV mutant was originally identified in a patient with severe growth impairment. The PV mutation is a C-insertion at codon 448 of the TRbeta gene and leads to a frame-shift of the carboxyl-terminal 14 amino acids of TRbeta1, resulting in total loss of triiodothyronine (T3) binding and transcriptional activation. PV was selectively expressed in the pituitary of the transgenic mouse and not in other tissues examined. The transgenic mice showed a significant impairment in weight gain. However, no changes in the serum level of thyroid-stimulating hormone were seen, and no elevation of thyroid hormones was detected in the transgenic mice. The circulating levels of growth hormone and insulin-like growth factor I were not affected in the transgenic mice, suggesting that the growth impairment in RTH is complex and is mediated by pathways that are yet to be elucidated.

Animals↗
PubMed1997

Split tolerance to the MHC class I molecule H-2Dd in animals transgenic for its soluble analog.

To determine whether the function of MHC molecules in tolerance and education is related to cell surface expression, we have produced two strains of transgenic mice in the C57Bl/6 background that express soluble analogs of the H-2D(d) class I protein. The transgenes were stably integrated and genetically transmitted in a Mendelian fashion. Messenger RNA for the hybrid genes was detected in all tissues analyzed in a class I-like pattern of expression, with the highest levels in lymphoid tissues. All mice bearing the transgenes expressed relatively high levels (0.1 mg/ml) of the encoded protein in their serum as assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Gel filtration chromatography showed that the soluble H-2D(d) protein exists as a heterodimer with beta2-microglobulin and as higher order multimers in serum. Lymphoid cells from the transgenic mice showed no cell surface expression of the soluble class I protein in indirect immunofluorescence assays. Splenocytes from two independently derived transgenic lines generated primary cytotoxic and proliferative responses directed against membrane H-2D(d) antigens. Mice of both strains rejected tail skin from donors that differed from the B6 background at the H-2D(d) locus only, but with delayed kinetics compared to nontransgenic littermate controls. Mice expressing the transgenic protein on immunization did not produce antibodies that recognized soluble H-2D(d) in ELISA, whereas B6 mice generated strong antibody responses to challenge with splenocytes bearing cell surface H-2D(d). Thus, transgenic mice expressing soluble H-2D(d) were partially tolerant to stimulation by membrane-bound H-2D(d). As with the activation of T-cells, the induction and maintenance of immunologic tolerance apparently displayed different requirements depending upon the T-cell subpopulation involved.

Animals↗
PubMed1996

Increased interleukin 4 and immunoglobulin E production in transgenic mice overexpressing NK1 T cells.

Natural Killer (NK)1.1+ (NK1) T cells are a specialized subset of alpha/beta T cells that coexpress surface receptors that are normally associated with the NK cell lineage of the innate immune system. On recognition of the conserved, major histocompatibility complex class I-like CD1 molecule, these cells are able to release explosive bursts of interleukin 4 (IL-4), a cytokine that promotes the T helper type 2 (Th2) effector class of an immune response. A unique feature of their T cell receptor (TCR) repertoire is the expression of an invariant TCR alpha chain, V alpha 14-J alpha 281, and of a restricted but polyclonal set of V beta gene families, V beta 8, V beta 7, and V beta 2. Here, we show that transgenic expression of this TCR alpha chain during thymic development is sufficient information to bias the differentiation of mainstream thymocytes towards the NK1 developmental pathway. It markedly increases the frequency of cells with the NK1 pattern of T cell differentiation and also has drastic consequences for the selection of the V beta repertoire. Transgenic CD4 cells exhibited a 10-100-fold increase in IL-4 production on mitogen stimulation in vitro and in vivo, and baseline levels of the Th2-controlled serum immunoglobulin isotypes, IgE and IgG1, were also selectively elevated in vivo.

Animals↗
PubMed1986

Placental immunoregulation.

Mammalian gestation is complex and varies widely among species, but the embryonic contribution to the maternal-fetal interface, the trophoblast, remains constant. Alloantigen and stage/tissue specific antigens are present on the trophoblast in low concentration and often in locations inaccessible to maternal immune effectors. Nonetheless, pregnancy does prime the mother for humoral immunity; cell-mediated responses are more difficult to demonstrate. The placenta appears to be an efficient block to cellular traffic into the fetus; the placental barrier to specific antibody has been established, but its efficiency is controversial. Nonspecific, local, active suppression mediated by lymphoid cells within the decidua is apparently an important concomitant of successful gestation. Yet there is evidence that an ongoing immune response is beneficial to pregnancy, allowing an increase in placental size in response to growth-promoting lymphokines while blocking graft-rejection mechanisms. Thus it appears that immunoregulation at the maternal-fetal interface is complex, and no single mechanism can account for the success of the "fetal allograft".

Animals↗
PubMed1985

Characterization of immune effector cells present in early murine decidua.

It has been suggested that murine decidual cells act as an important immunoregulatory population localized to the pregnant uterus. We have examined early murine decidua to determine if immune effector cells occur in the decidual environment in proximity to the conceptus. High levels of natural killer (NK) cell activity were found consistently in decidual cell suspensions with peak activity occurring on Day 6.5 of gestation. NK activity declined as pregnancy proceeded and was not significant by Day 12.5 of gestation. Decidual cell suspensions did not appear to contain significant numbers of functional B or T effector cells. No antipaternal T-cell response could be demonstrated even in the decidua of immune mice. Lack of T-cell responses was attributed to the absence of T cells from decidua rather than to their inactivation because precursors of cytotoxic T lymphocytes (pCTL) could not be detected in decidual cell suspensions. Furthermore, the levels of pCTL detectable in spleen cell suspensions could not be reduced by mixing spleen cells with 7.5-day decidual cells. These results suggest that B cells and T cells may not occur in early decidua while NK cells are present and regulated independently.

Animals↗
PubMed1984

Placenta as a selective barrier to cellular traffic.

Transplacental passage of cells from mother to fetus during murine pregnancy was examined by using glucose phosphate isomerase (GPI) or fluorescein tagging as markers. Female mice of strains (BALB/cCr X C3H/HeJ)/F1 or (A/J X C57BL/6J)F1 (both Gpi-1a/b) were mated to the corresponding Gpi-la males (BALB/cCr or A/J, respectively). Cells of the liver, blood, and/or spleen in the offspring were typed at days 15, 16, 17, or 18 of gestation, the day of delivery, or 1 day postpartum. Only two of 172 Gpi-1a/a mice obtained from these matings showed evidence of maternal cell trafficking. Sensitivity of the assay was 1% Gpi-1a/a population. Fluorescein-labeled BALB/cCr peripheral red blood cells (RBC) or white blood cells (WBC) were injected i.v. into syngeneically mated BALB/cCr mothers on day 18. After 24 hr, the blood or liver of the neonates was formalin-fixed and examined in the fluorescence-activated cell sorter (FACS). Some RBC crossed the placenta, but WBC were usually not detected in fetal liver in significant numbers. This technique was very sensitive, and we estimated that no more than 225 WBC could enter the fetus via this route. Thus, we conclude that passage of significant numbers of maternal WBC into the fetus is rare, and perhaps this passage is related to a placental abnormality.

Animals↗
PubMed1980

Differential expression of minor histocompatibiility antigens on the surface of the mouse oocyte and preimplantation developmental stages.

The expression of specific minor histocompatibility antigens on oocytes and preimplantation developmental stages in the mouse has been examined using immunofluorescence. Multi-specific alloantisera in conjunction with serological adsorption and target cells of the appropriate genotype have been used to how that there is differential expression of minor histocompatibility antigens during early development. Detailed analysis showed that antigen expression can be detected on oocytes and zygotes, but not on two-cell stages. From the eight-cell stage to the blastocyst, reactivity with antibody directed against a single specificity could be detected.

Adsorption↗
PubMed1980

Apparent destruction of bovine blood group determinants by chymotrypsin.

Although chymotrypsin treatment eliminated the reactivity of many antigenic determinants on the bovine red cell, haemolytic inhibition tests, double diffusion in agar tests, and immunizations provided no conclusive evidence of any of the affected determinants in the soluble digest. Chymotryptic digestion unmasked an apparent cryptantigen, rendering Q-positive cells reactive with a previously Q-negative anti-serum.

Animals↗