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P Res

Publications and source records attributed to P Res.

15 recordsLinked to original sources
PubMed2000

Birth after treatment of a male with seminoma and azoospermia with cryopreserved-thawed testicular tissue.

The case of an infertile couple in which a testicular seminoma and azoospermia were discovered in the husband during infertility treatment is described. A small piece of testicular tissue, obtained by biopsy from the healthy testis [testicular sperm extraction (TESE)], was deep-frozen before oncology therapy was initiated. The patient's lymphocyte karyotype was normal and no Y microdeletions were found. After conclusion of oncology treatment, the tissue was thawed and successfully used in the intracytoplasmic sperm injection (ICSI) procedure. A healthy girl was born. Testicular tumours are known to impair fertility in the majority of patients, and fertility deteriorates further after cytotoxic and surgical oncology treatment. Until recently in Slovenia, for young oncology patients cryopreservation was applied only to high quality ejaculate fulfilling the criteria for intrauterine insemination or in-vitro fertilization after thawing. Failing that, the only remaining options were fertilization by donor spermatozoa or child adoption. New assisted reproductive technologies, of which the ICSI procedure is the most successful, are suitable for the treatment of only the most severe cases of male infertility. It is reasonable to cryopreserve even poor quality ejaculate prior to the oncology therapy, as well as testicular tissue in cases of azoospermia.

Adult↗
PubMed1999

Developmental stages in the human thymus.

The thymus is populated by hematopoietic cells that have the capacity to develop into at least three different hematopoietic lineages, T, NK and dendritic cells. While developing into T cells these cells pass a series of developmental stages that can be discriminated on the basis of expression of a number of antigens. The availability of a myriad of monoclonal anti- bodies against human differentiation antigens has permitted a detailed analysis of the various cellular stages in the human thymus. This analysis not only comprised investigation of molecular but also of functional features of purified thymocyte subsets, since more recently assays were set up that allowed investigation of the hematopoietic precursor activities of human thymic progenitor cells. Here we review the current status of knowledge with regard to early developmental stages in the human thymus. In addition, we discuss recent data on later developmental stages, in particular concerning positive selection and maturation of T cells.

Antigens, Differentiation↗
PubMed1998

Characterization of CD34+ thymic stromal cells located in the subcapsular cortex of the human thymus.

In this paper we report that suspensions of human fetal thymocytes contain cells that express high levels of CD34 and Thy-1. These cells were characterized with regard to location within the thymus, phenotype, and function. Confocal laser scan analysis of frozen sections of fetal thymus with anti-CD34 and Thy-1 antibodies revealed that the double-labeled cells were located in the pericortical area. In addition, it was found that the CD34+Thy-1+ cells lacked CD45 and CD50, indicating that these cells are not of hematopoietic origin; this was confirmed by the finding that these cells could be cultured as adherent cells in a medium with cholera toxin and dexamethasone, but failed to grow in mixtures of hematopoietic growth factors. Further analysis indicated that most cultured CD34+Thy-1+ cells expressed cytokeratin (CK) 14 but lacked CK 13, suggesting that these cells are immature epithelial cells. Cultured CD34+Thy-1+ cells were able to induce differentiation of CD1-CD34+CD3-CD4-CD8- thymic precursors into CD4+CD8+ cells in a reaggregate culture in the absence of exogenous cytokines. The CD4+CD8+ cells that developed in these cultures did not express CD3, indicating that CD34+Thy-1+ thymic stromal cells are not capable of completing full T cell differentiation of thymic hematopoietic progenitor cells.

Cell Differentiation↗
PubMed1997

Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells.

The presence of T and NK cells in the human fetal liver and the fact that fetal liver hemopoietic progenitor cells develop into T and NK cells suggest a role for the fetal liver compartment in T and NK cell development. In this work, we show that the capacity of fetal liver progenitors to develop into T cells, in a human/mouse fetal thymic organ culture system, is restricted to an immature subset of CD34+ CD38- cells. No T cell-committed precursors are contained within the more differentiated CD34+ CD38+ population. This conclusion is supported by the observations that no TCR-delta gene rearrangements and no pre-TCR-alpha expression can be detected in this population. However, NK cells were derived from CD34+ CD38- and CD34+ CD38+ fetal liver cells cultured in the presence of IL-15, IL-7, and Flt-3 ligand. Eighty to ninety percent of cells arising from the CD34+ CD38+ population expressed the NK cell-associated markers CD56, CD16, CD94, and NKR-P1A. Several subpopulations of NK cell precursors were identified by differential expression of these receptors. Based on the detection of populations with a similar antigenic profile in freshly isolated fetal liver cells, we propose a model of NK cell differentiation. Collectively, our findings suggest that CD34+ cells differentiate into NK cells, but not into mature T cells, in the human fetal liver.

Animals↗
PubMed1997

Prethymic CD34+ progenitors capable of developing into T cells are not committed to the T cell lineage.

Progenitor cells that seed the fetal thymus are derived from the fetal liver and the bone marrow. These cells migrate through the fetal blood to the thymus. In this work, we address which peripheral progenitor cells have the potential to become T cells and whether these progenitor cells are already committed to the T cell lineage. All CD34+CD38- precursor cells, regardless of their origin, are able to develop into T cells in a hybrid human/mouse fetal thymic organ culture. Previously, we found that the more differentiated CD34+CD38+ progenitor cells from fetal liver cannot develop into T cells. In this work, we show that CD34+CD38+ cells from fetal bone marrow and cord blood are capable of T cell development. In spite of the T cell-developing potential, we did not detect rearrangements of TCR-delta or TCR-beta loci in any of the CD34+ peripheral precursors. CD34+ fetal bone marrow cell subpopulations express pre-TCR-alpha. However, we could not detect expression of pT alpha or of recombination-activating gene 1 in CD34+ cord blood cells. Since cord blood CD34+ cells should contain the direct progenitors of the CD34+ thymocytes, our data do not support the notion that in humans commitment to the T cell lineage occurs before the cells migrate into the thymus.

Animals↗
PubMed1997

Identification of a committed T cell precursor population in adult human peripheral blood.

Here, we report data concerning the discovery in adult human peripheral blood of a precursor cell population able to differentiate into CD4+CD3+ alpha beta + mature T cells. These cells, which represent 0.1-0.5% of total peripheral blood mononuclear cells (PBMC), express substantial levels of CD4, but lack CD3 surface expression. At a molecular level, they express the pre-T cell receptor alpha (pT alpha) gene, CD3-gamma, CD-delta and CD-epsilon, and RAG-1 recombination enzyme and have initiated rearrangements in the T cell receptor (TCR)-beta locus (D-J). Moreover, low levels of CD3 epsilon protein, but not of TCR-beta chain, can be detected in their cytoplasm. Our results suggest that CD4+CD3- cells identified in peripheral blood are different from CD3-CD4+CD8- thymocytes and may contain precursors of an extrathymic T cell differentiation pathway.

Adult↗
PubMed1997

Downregulation of CD1 marks acquisition of functional maturation of human thymocytes and defines a control point in late stages of human T cell development.

We have investigated whether in the human thymus transition of CD4+CD8+ double positive (DP) to CD4+ or CD8+ single positive (SP) cells is sufficient for generation of functional immunocompetent T cells. Using the capacity of thymocytes to expand in vitro in response to PHA and IL-2 as a criterion for functional maturity, we found that functional maturity of both SP and DP thymocytes correlates with downregulation of CD1a. CD1a- cells with a persistent DP phenotype were also found in neonatal cord blood, suggesting that at least a proportion of mature DP cells can emigrate from the thymus. The requirements for generating functional T cells were investigated in a hybrid human/mouse fetal thymic organ culture. MHC class II-positive, but not MHC class II-negative, mouse thymic microenvironments support differentiation of human progenitors into TCR alpha beta+CD4+ SP cells, indicating that mouse MHC class II can positively select TCR alpha beta +CD4+ SP human cells. Strikingly, these SP are arrested in the CD1a+ stage and could not be expanded in vitro with PHA and IL-2. CD1a+CD4+ SP thymocytes do not represent an end stage population because purified CD1a+CD4+ SP thymocytes differentiate to expandable CD1a- cells upon cocultivation with human thymic stromal cells. Taken together these data indicate that when CD1a+ DP TCR alpha beta low cells mature, these cells interact with MHC, but that an additional, apparently species-specific, signal is required for downregulation of CD1a to generate functional mature TCR alpha beta + cells.

Aging↗
PubMed1996

CD34+CD38dim cells in the human thymus can differentiate into T, natural killer, and dendritic cells but are distinct from pluripotent stem cells.

Recently we reported that the human thymus contains a minute population of CD34+CD38dim cells that do not express the T-cell lineage markers CD2 and CD5. The phenotype of this population resembled that of CD34+CD38dim cells present in fetal liver, umbilical cord blood, and bone marrow known to be highly enriched for pluripotent hematopoietic stem cells. In this report we tested the hypothesis that the CD34+CD38dim thymocytes constitute the most primitive hematopoietic cells in the thymus using a combination of phenotypic and functional analyses. It was found that in contrast to CD34+CD38dim cells from fetal liver and bone marrow, CD34+CD38dim cells from the thymus express high levels of CD45RA and are negative for Thy-1. These data indicate that the CD34+CD38dim thymocytes are distinct from pluripotent stem cells. CD34+CD38dim thymocytes differentiate into T cells when cocultured with mouse fetal thymic organs. In addition, individual cells in this population can differentiate either to natural killer cells in the presence of stem cell factor (SCF), interleukin-7 (IL-7), and IL-2 or to dendritic cells in the presence of SCF, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha(TNFalpha), indicating that CD34+CD38dim thymocytes contain multi-potential hematopoietic progenitors. To establish which CD34+ fetal liver subpopulation contains the cells that migrate to the thymus, we investigated the T-cell-developing potential of CD34+CD38dim and CD34+CD38+ fetal liver cells and found that the capacity of CD34+ fetal liver cells to differentiate into T cells is restricted to those cells that are CD38dim. Collectively, these findings indicate that cells from the CD34+CD38dim fetal liver cell population migrate to the thymus before upregulating CD38 and committing to the T-cell lineage.

ADP-ribosyl Cyclase↗
PubMed1991

Heat-shock proteins and autoimmunity in humans.

T cells and antibodies against self and non-self hsp are present in both patients and healthy controls. T cells responding to hsp65 can be involved in autoimmune diseases, this was demonstrated for two site-specific animal autoimmune diseases: AA in Lewis rats and diabetes (IDDM) in NOD mice. In human ReA there is evidence for a direct stimulation of joint T cells by antigens of the organisms causing the infection which precedes the joint inflammation. The individual antigens of the triggering bacteria still have to be defined, but hsp65 may be of importance since this is one of the molecules recognized by synovial T cells in ReA patients. In RA there are no clear data implicating an infection in the initiation of joint inflammation, but mycobacteria have been suggested to be involved. We have discussed experimental findings which are in favor of, or in contradiction with, a role of mycobacterial antigens--particularly hsp65--in the etiology of RA. T cells recognizing hsp65 and other mycobacterial antigens are present in the joint, but there is no indication for a specific involvement of one or a limited set of (myco)bacterial antigens in the pathogenesis of RA.

Animals↗
PubMed1987

Nickel-specific T lymphocyte clones derived from allergic nickel-contact dermatitis lesions in man: heterogeneity based on requirement of dendritic antigen-presenting cell subsets.

Inflammatory skin T cells were cloned in an antigen-independent way from lesions of patients with experimentally induced nickel-contact dermatitis. In three experiments 7-15% of the CD4+8- T lymphocyte clones (TLC) appeared to be specific for nickel in a proliferation assay. These proliferative response of nickel-specific TLC required the presence of antigen-presenting cells (APC) and were restricted by HLA class II molecules. All TLC recognized nickel presented by APC from epidermal skin. Remarkably, 5 out of 8 nickel-specific TLC exclusively recognized nickel when presented by these skin-specific APC whereas 3 out of these 8 clones could also recognize nickel presented by APC from peripheral blood. The critical APC within the fractions of epidermal cells and peripheral blood appeared to belong to the family of dendritic cells, i.e. Langerhans cells and circulating dendritic cells, respectively.

Antigen-Presenting Cells↗
PubMed1987

Colonization of human genital tract by Streptococcus agalactiae.

This bacteriological study involved 92 young married couples who required medical help because of infertility. Colonization of male urethra or the presence of Streptococcus agalactiae in the ejaculate was detected in 9.78% of men. Vagina or vagina and cervix were colonized in 4.35% of women. Oral application of phenoxymethylpenicillin temporarily eliminated S. agalactiae from the genital tract of all colonized partners. Repeated colonization occurred 3-7 months later, in three cases by different serotypes compared with pretreatment period, in one case by the same serotype.

Adult↗
PubMed1987

The crucial role of human dendritic antigen-presenting cell subsets in nickel-specific T-cell proliferation.

In the majority of patients, allergic nickel contact dermatitis is associated with a proliferative response of peripheral blood T lymphocytes to nickel sulfate. Optimal proliferation was found in a concentration range of 1-2 X 10(-4) M nickel sulfate. Nickel-specific response of purified peripheral blood T cells requires the presence of antigen-presenting cells (APC). Both peripheral blood monocytes and skin-derived epidermal cells could function as APC, but epidermal cells were shown to be more potent than monocytes. By testing FcR+ monocytes and FcR- circulating dendritic cells for their antigen-presenting capacities, it was found that the critical APC within the fraction of monocytes is the circulating dendritic cell. Testing highly purified T6+ (CD 1) skin-specific dendritic cells (Langerhans cells, LC) and T6- epidermal cells as APC, the critical APC within the fraction of epidermal cells appeared to be the LC. The crucial role of LC was stressed in experiments using T cells from patients exhibiting a positive patch test to nickel but a low or absent proliferative response to nickel by unpurified peripheral blood cells. Whereas addition of peripheral blood APC was ineffective, addition of LC to purified peripheral T cells was shown to overcome this low responsiveness to nickel. These results indicate the crucial role of dendritic APC subsets in nickel-specific T-cell proliferation.

Antigen-Presenting Cells↗
PubMedDate not supplied

[Sterilization of the male].

The authors describe conditions in the field of sterilization in Slovenia from July 1977 to December 1979 in view of the new law on medical measures for the realization of the right to free decision on the birth of children. During this time 163 females and 62 males were sterilized. A general approach to sterilization is described, as well as the results of vasectomy.

Adult↗