Biomedical subjects

W Haas

Publications and source records attributed to W Haas.

187 records · Page 11Linked to original sources

PubMedDate not supplied

Selection of the T-cell repertoire during ontogeny.

This report examines conflicting hypotheses concerning T-cell repertoire selection in terms of H-2 restriction during ontogeny. The experiments described in this report were incompatible with the hypothesis that bias in the repertoire is solely a consequence of "more or less intentional priming" by foreign antigen. Rather, results indicate that the repertoire is selected by self major histocompatibility complex (MHC) antigens in the absence of foreign antigens. Allorestricted T cells, the existence of which was previously thought to be incompatible with the concept of complete repertoire selection by self MHC antigens, were shown to significantly cross-react on targets expressing self MHC antigens. Thus, it is possible that allorestricted T cells are simply cross-reactive T-cell clones restricted by self MHC antigens; indeed, all experimental data were compatible with the idea of complete selection of the T-cell repertoire in terms of H-2 restriction by self MHC antigens.

Animals↗

PubMedDate not supplied

Limited diversity of the rearranged T-cell gamma gene.

The immunoglobulin-related, T-cell specific gamma gene is rearranged in a wide variety of murine T lymphocytes. We detected gamma-gene transcripts in all cloned cytotoxic T lymphocytes examined but in only 1 of 11 T-helper cell lines or hybridomas. Although in cytotoxic T cells, the rearranged gamma gene seems to have been assembled from the same germ-line variable and joining gene segments, the transcribed gene exhibited distinct sequence diversity near the junction between these segments.

Amino Acid Sequence↗

PubMedDate not supplied

Absence of growth by most receptor-expressing fetal thymocytes in the presence of interleukin-2.

The growth of mature T cells is regulated by receptors for interleukin-2 (IL-2) and by IL-2 itself. Binding of antigen to T-cell antigen receptors induces the expression of IL-2 receptors, and binding of IL-2 to these receptors induces transferrin receptor expression and is sufficient to promote the growth of T cells for several days. However, nothing is known about the growth requirements of pre-T cells. We have therefore studied the dividing population of T-cell precursors which carry the Thy-1 surface antigen, but lack surface antigens Ly2 and L3T4; these cells are present in 14-day-old embryonic thymus. If the thymus is removed at this stage and placed in organ culture, all lymphocyte subpopulations normally present in thymuses of adult mice develop in vitro, that is, the nonfunctional Ly2+, L3T4+ population and the functional Ly2+, L3T4- and Ly2-, L3T4+ populations. We now report that, in contrast to their progeny, the early Ly2-, L3T4- cells express large amounts of IL-2 receptors, but most of them do not grow in IL-2-containing media outside the thymus. In contrast to dividing mature T cells, most fetal thymocytes express low amounts of transferrin receptors.

Animals↗

PubMedDate not supplied

Transfer of specificity by murine alpha and beta T-cell receptor genes.

T-cell receptor alpha- and beta-chain genes were isolated from a class I major histocompatibility complex-restricted cytotoxic T-cell clone and transferred by protoplast fusion into another cytolytic T-cell clone of different specificity. Expression of the transfected alpha and beta genes endowed the recipient cell with the specificity of the donor cell.

Alleles↗

PubMedDate not supplied

Transfection of the CD8 gene enhances T-cell recognition.

Antibodies against CD8 or CD4 antigens can prevent T-cell functions induced by T-cell targets. As CD8 or CD4 antibodies can also initiate negative signals in T cells in the absence of appropriate targets it is not clear whether CD8 and CD4 molecules are directly involved in the interaction of T cells with their targets. In previous experiments we have introduced the T-cell receptor alpha- and beta-chain genes from a CD8-positive cytolytic T cell specific for the antigen fluorescein (FL) and the H-2D molecule of the major histocompatibility complex (MHC) into a CD8-negative recipient cell. The CD8-positive donor cell lysed both FL-conjugated fibroblasts and lymphoblasts, which express relatively high and low amounts of H-2D molecules, respectively. In contrast the CD8-negative transfectant lysed FL-conjugated fibroblasts only. Here we show that recognition of FL-conjugated lymphoblasts by the transfectant is enhanced by supertransfecting it with the CD8 gene.

Animals↗

PubMedDate not supplied

Exercise-induced hypoglycaemia and subcutaneous insulin infusion.

To assess whether exercise-induced hypoglycaemia could be prevented by interruption of insulin infusion (3 h) we studied diabetic patients treated with continuous subcutaneous insulin infusion (CSII). The studies were performed in 7 insulin-dependent diabetics (aged 31.4 +/- 4.8 (mean +/- SD) years, duration of diabetes 16.9 +/- 5.4 years), after an overnight fast and in the afternoon, 4 h after the last pre-meal bolus injection (exercise and control period). Bicycle exercise (45 min at 60% of maximum oxygen consumption) was started 30 min after the insulin infusion was stopped. During exercise there was a more pronounced decline in blood glucose in the afternoon (2.2 +/- 0.3 mmol/l, mean +/- SEM) than in the morning (1.4 +/- 0.4 mmol/l) (p less than 0.01). This corresponded to higher mean levels of free insulin during exercise in the afternoon (20 +/- 4.5 mU/I vs 12.0 +/- 1.0 mU/l, in the morning). Interruption of insulin delivery for 3 h resulted in a moderate increase of blood glucose, a gradual decrease of free insulin, and a moderate increase in free fatty acids and beta-hydroxybutyrate. During exercise in the afternoon 3 diabetics suffered from symptomatic hypoglycaemia (BG less than 2.8 mmol/l). In contrast with most of the other patients they showed no decline of free insulin during exercise. Thus even after interruption of basal rate insulin infusion moderate postprandial exercise may lead to hypoglycaemia if there is relative hyperinsulinism.

Adult↗

PubMedDate not supplied

Glutamine peptide does not improve gut barrier function and mucosal immunity in total parenteral nutrition.

In two separate experiments, three groups of 10 (first experiment) and 12 (second experiment) rats each were catheterized for the long term via the right jugular vein and fed one of the following dietary regimens for 7 days while in individual metabolism cages. The rat food control groups were fed powdered rat food. The total parenteral nutrition (TPN) formula for one group was enriched with the stable dipeptide L-alanyl-L-glutamine (ALA-GLN) equivalent to a 1% or 2% glutamine concentration. For the control TPN groups, the dipeptide was replaced by isonitrogenous amounts of alanine (ALA). In both experiments, bacterial translocation was promoted to a similar extent by the ALA-GLN and ALA TPN formulas compared with the rat food groups. Bacterial overgrowth in the cecum and intestinal atrophy, quantitated by the mucosal protein content, did not differ between ALA-GLN and ALA groups. The nitrogen balances of the three groups showed similar values in the second experiment. The secretory immunoglobulin A was measured in washings of the jejunum and ileum (soluble fraction) and in the homogenates of the gut mucosa (insoluble fraction). The secretory immunoglobulin A values of both fractions showed no difference between the ALA and ALA-GLN groups, irrespective of whether they were normalized for gut segment length or corrected for mucosal protein content. In conclusion from these results, the supplementation of TPN with glutamine does not seem to improve gut barrier function or mucosal immunity in unstressed rats.

Alanine↗