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F Triebel

Publications and source records attributed to F Triebel.

At least 55 records · Page 3Linked to original sources
PubMed1986

Sequences and diversity of human T cell receptor beta chain variable region genes.

The nucleotide sequences of 22 human T cell antigen receptor (TcR) beta chain variable region genes isolated from various T lymphocytes have been analyzed. Of the 19 variable gene segment (V beta)-containing sequences, 17 were unique. The V beta gene segments were grouped into 11 families. Comparisons were made with the data of Concannon et al. to unify the nomenclature. The data is consistent with a total V beta gene segment repertoire with a most probable value of 38 members and an upper bound of 104 members at the 95% confidence level. Southern blot data of germline DNA using selected TcR V beta cDNAs as probes support this estimate. The human repertoire is approximately three to four times greater than that reported for the mouse. Explanations for this discrepancy are proposed.

Base Sequence↗
PubMed1986

Media conditioned by human leukemic T-cells induce expression of IL2 receptors and proliferation of normal T lymphocytes.

Peripheral blood T-colony-forming cells (T-CFC) from patients with T-cell acute lymphoblastic leukemias (T-ALL) and T-cell non-Hodgkin lymphomas (T-NHL) can generate colonies in methylcellulose in the absence of added growth factors and/or mitogenic stimulation. In the present study, we show that media conditioned (LCM) by unstimulated mononuclear cells (MNC) from these patients can induce proliferation (proliferating inducing activity; PIA) and promote colony growth (T-cell colony promoting activity; T-CPA) of normal T lymphocytes in the absence of any other mitogenic stimulation. Preincubation of normal E+ lymphocytes with some TCPA+, PIA(-)-LCM for 48 hr leads to IL2-induced cell proliferation in the absence of any other stimulation. Moreover, staining of the cells with anti-Tac monoclonal antibody (Mab) reveal 9%-26% Tac+ cells. Both PIA and IL2 receptor-inducing activities were abrogated by treatment of LCM with proteolytic enzymes or by heating at 47 degrees C for 30 min. Modulation of the T3 molecule by OKT3 MAb on normal E+ cells did not abrogate the capacity of LCM to induce expression of IL2-receptors, suggesting that this activity was not mediated by triggering the Ti-T3 molecular complex. These activities were detected in media conditioned by both unfractionated MNC and blast-enriched cell fractions, and their production required DNA and RNA synthesis by actively dividing cells. Taken together, these findings indicate that human leukemic T cells spontaneously release activities which can activate normal resting T lymphocytes.

Antibodies, Monoclonal↗
PubMed1986

Immune response to diphtheria toxin and to different CNBr fragments: evidence for different B and T cell reactivities.

The antigenic structure of the diphtheria toxin has been studied in man. B and T cell responses to diphtheria toxoid and to different fragments of the toxin molecule were analyzed in 4 individuals one month after booster immunization. Studies on the B cell response showed that: part of the response was directed against assembled topographic sites; 80% of the response was directed against determinants present on fragment A; the few determinants present on the CNBr peptides of B cross-react with determinants present on A; and reduction of the second disulfide bridge of fragment B diminishes the response. In contrast to the antibody response, most of the T cell reactivity was directed against the B fragment or CNBr peptides from this fragment. Analysis of the fine specificity of T lymphocyte clones revealed that some CNBr fragments share common T cell determinants. These studies indicate that T and B cell determinants are differently distributed on the molecule and that large cross-reactivities that are not explained by the analysis of the amino acid sequence could be found at the B and T cell level.

Antibody Formation↗
PubMed1986

T-cell colony formation in patients with T-cell malignancies: growth factor requirements for in-vitro proliferation of peripheral blood T-cell colony-forming cells.

Peripheral blood T colony-forming cells (T-CFC) from patients with T-cell malignancies are capable of proliferation in methylcellulose, in the absence of added growth factors or mitogenic stimulation. We show here that based on the spontaneous plating efficiencies of their T-CFC, two groups of patients can be established: Group A (10 patients) with a high colony number (more than 100 colonies/10(5) seeded cells), and group B (12 patients) with less than 100 colonies/10(5) cells. The addition of interleukin 2-(IL2) containing PHA-leukocyte conditioned medium enhanced colony growth from group B but not group A patients. Moreover, both biochemically purified and recombinant IL2 induced the colony growth from group B but not group A patients without any other stimulation. In addition, a monoclonal antibody (moAb) against the IL2 receptor (IL2-R; anti-Tac) inhibited the spontaneous colony formation from T-CFC of both groups of patients. These observations strongly suggest that IL2-R are involved in the spontaneous colony growth of T-CFC. To determine whether IL2 is also involved in the spontaneous colony formation, media conditioned (LCM) by unstimulated leukemic cells were tested for IL2 activity. A constitutive release of IL2 was detected in LCM from only 2 out of 10 patients tested, and some of them were capable to inhibit thymidine incorporation by IL2-dependent cells cultured in the presence of highly purified IL2. However, most of these LCM contained a T-cell colony-promoting activity (TCPA) inducing colony formation from both normal resting and PHA-stimulated E+ clonogenic cells without added IL2 or mitogenic stimulation. TCPA-containing LCM induced the expression of functional IL2-R and IL2 release by normal resting lymphocytes. TCPA was constitutively released by blast-enriched cell fractions suggesting that it is released by the leukemic cells.

Antibodies, Monoclonal↗
PubMed1986

Expression of MHC class II and Tac antigens on IL2-activated human T cell clones that can stimulate in MLR, AMLR, PLT and can present antigen.

The expression of interleukin 2 (IL2) receptor and HLA-DR, DQ, and DP antigens on the surface of four diphtheria toxoïd (DT)-specific T lymphocyte clones (TLC) and two TLC specific for an allogeneic EBV-transformed cell line was investigated with the use of monoclonal antibodies (MoAbs) that recognize defined molecules or epitopes. Incubation of a resting TLC with IL2 resulted in a 10- to 30-fold increase in the level of DR, DQ, and Tac antigen expression. On the other hand, incubation of an activated TLC with IL2 decreased for 1 to 6 hr the level of expression of these three antigens. Anti-FA MoAbs did not react with any of the TLC tested suggesting that the expression of DR, DQ, and DP antigens is dissociated on activated TLC. Surface-marker analysis with anti-DR MoAbs indicated that DR epitopes were differently expressed at some activation stages of the TLC. Functional studies showed that activated TLC can stimulate in MLR, AMLR, and PLT. These proliferative responses were inhibited by preincubating the TLC with anti-DR MoAbs suggesting that the stimulatory determinants were predominantly DR molecules. In addition, some TLC can act as antigen presenting cells in DT-specific proliferative responses. These results indicate that MHC class II molecules on activated T lymphocytes may be relevant for the control of specific immunologic responses in vivo.

Antibodies, Monoclonal↗
PubMed1986

CD 1-8 antigens on human diphtheria toxoid T lymphocyte clones: expression and modulation by TPA, sodium butyrate, and 5-azacytidine.

The modulation of antigen expression on the surface of TLC by different differentiation inducers as well as the inhibition of the TLC proliferative response by specific MoAbs may lead to a clarification of the role of various surface molecules studied in antigen-specific T-cell response. We investigated the expression of CD 1-8 antigens on the surface of diphtheria toxoid or varidase specific TLC with a series of MoAb. CD1 and CD8 antigens were not expressed on the proliferative TLC. CD2, CD3, CD4, and CD5 antigens were homogeneously expressed on all TLC in contrast to CD6 and CD7 antigens which were present on only a fraction of the cells in a given TLC. In functional assays, anti-CD2, anti-DR VI-15C, and anti-CD25 MoAbs blocked the proliferative response to DT and anti-CD3, anti-CD4, anti-D44 MoAbs had intermediate inhibition effects. Anti-CD5, anti-CD6, and anti-CD7 MoAbs did not inhibit the proliferative response. Surface marker analysis revealed that the expression of CD2 to CD7 antigens (and also CD25) may be modified following incubation of the TLC with TPA or sodium butyrate but not with 5-azacytidine. TPA greatly decreased the expression of CD3 and CD4 antigens after a 6-hr exposure. Preincubation of TLC cells with TPA inhibited the mitogenic effect of anti-CD3 MoAbs on TLC cells in proliferative assays, but did not inhibit their capacity to proliferate in response to DT despite low levels of CD3 and CD4.

Antibodies, Monoclonal↗
PubMed1985

T-lymphocyte progenitors in man: phenotypic characterization of blood and bone marrow T-colony forming cells.

Human T-lymphocyte cell precursors are driven to proliferate in vitro and to form T-cell colonies during incubation with a PHA-stimulated lymphocyte supernatant (P-SUP). By using cell affinity chromatography, we selected different populations of putative T-lymphocyte precursors in the blood and bone marrow. T-colony forming cells (T-CFC) were found in each of these different populations of cells with phenotypically immature cell surface markers: OKT11- cells or OKT4-/OKT8- cells in the blood and bone marrow, and OKT10+ or RFB-1+ cells in the bone marrow. Pretreatment with OKT3, together with a monoclonal anti-DR antibody and complement, did not abrogate the T-colony forming capacity. The OKT4-/OKT8- precursors were more radiosensitive (Do = 105 rads) than OKT4+, OKT8+ cells (Do = 360 rads) in their T-colony forming capacity. These results suggest that T-CFC could be induced to grow in agar from cells populations representing early steps of the T-cell lineage.

Aged↗
PubMed1984

Antigen-specific proliferative human T cell clones with specificity for diphtheria toxoid: genetic and molecular restriction by class II antigens.

Human T lymphocyte clones (TLC) specific for diphtheria toxoid (DT) were isolated from a DR6/7 individual by cloning in soft agar in vivo sensitized T lymphocytes. We report here the isolation and characterization of 3 of these clones by studying: (a) the kinetic of activation, (b) the surface phenotypes, (c) the fine specificity for one of the 2 DT chains and (d) the genetic restriction of the proliferative response by the haplotype DR7. Moreover, blocking studies of the proliferative response to DT by various immunochemically characterized anti-HLA-DR monoclonal antibodies indicate that, on the DR7 molecule, more than one Ia determinant may participate in the clonal DT proliferative response. By using human TLC of a defined specificity and well-characterized anti-DR monoclonal antibodies, such studies may help to define the functional repertoire of Ia molecules in man.

Clone Cells↗
PubMed1984

Differential inhibition of human antigen-specific T cell clone proliferative responses by distinct monoclonal anti-HLA-DR antibodies.

The inhibition of diphtheria toxoid and varidase-specific T cell clones from a single DR 6/7 donor by eight distinct monoclonal anti-HLA-DR antibodies was tested in proliferative assays. These moAb were selected because they had been previously defined for their ability: 1) to react with Ia molecules; 2) to recognize similar or different epitopes; 3) to share or not share idiotypic specificities. Our results show a distinct inhibition pattern for each clone tested. Furthermore, the various moAb could be classified into three groups according to their inhibitory effect on T cell proliferation. These data suggest: a) an epitopic restriction by class II antigens of antigen-specific human T cell clone proliferation; and b) the recognition of functional epitopes on the human Ia-like antigens by some but not all moAb studied.

Antibodies, Monoclonal↗
PubMed1984

T-lymphocyte progenitors in man: biochemical characterization of a colony promoting activity (CPA) active on immature precursors.

PHA-stimulated lymphocyte supernatants (P-SUP) containing colony promoting activity (CPA) and interleukin-2 (IL-2) were found to drive T-lymphocyte precursor cells (OKT4-OKT8- blood cells) into colonies of mature T cells in agar. Ammonium sulphate precipitation followed by gel filtration on Sephadex G-75 showed that both IL-2 activity and CPA coeluted in the 21,000 MW fraction. Chromatofocusing on a PBE 94 gel equilibrated between pH 7.4 and 4.2 showed that CPA coeluted with the two main peaks of IL-2 (pI 7.2, pI 6.7). Adsorption of IL-2 activity by more than 97% on different T-cell lines did not completely abolish CPA. These results suggest that other(s) factor(s) with the same biochemical characteristics as IL-2 play a role in the induction of growth and differentiation of immature T-cell precursors.

Cell Differentiation↗
PubMed1983

Interleukin-2 production after blood transfusions in prospective kidney transplant recipients.

We have investigated whether suppression of the allogeneic response after blood transfusion (BT) could be due to inhibition of the production or activity of Interleukin-2 (IL-2), a soluble mediator involved in T lymphocyte proliferation. Reduction of IL-2 production after BT was less frequent than, but significantly associated with, non specific MLR suppression. However, MLR suppressor cells did not inhibit the release of IL-2 from autologous pre-BT lymphocytes. In addition, post-BT soluble suppressor factors of the MLR did not affect the ability of IL-2 to promote cell proliferation. Thus, although MLR suppression after BT is associated with reduced IL-2 production, this is not a major mechanism involved in this effect.

Blood Transfusion↗
PubMed1981

Pure erythrocytosis: reappraisal of a study of 51 cases.

Fifty-one cases of pure, primary erythrocytosis were identified and followed at Hôpital Saint-Louis, Paris, and compared with 350 cases of polycythemia vera (PV) observed during the same period. At the initial evaluation, these cases did not differ from PV cases with respect to age, sex ratio, degree of red cell volume increase, and clinical symptoms. They did differ by the absence of splenomegaly, granulocytosis and thrombocytosis. At a late stage of evolution only a few cases developed classical criteria of PV. From this group of apparently homogeneous cases, two subgroups evolved. Sixty percent of the cases were highly responsive to myelosuppression with 32P. The median duration of the first remission was greater than five years, the mean yearly dose of 32P was very low, and there was a low incidence of complications. The other group (40% of cases) was relatively resistant to myelosuppressive agents. The development of better methods of investigate this disorder might help in discriminating these two groups from both an etiological and pathophysiological viewpoint. The thromboembolic risk of these diseases suggests that myelosuppressive therapy should be utilized in older patients with higher risk of vascular accidents, reserving phlebotomy for younger patients and those who are shown to be resistant to 32P therapy.

Adolescent↗
PubMed1981

Characterization of the T lymphocyte colony-forming cells and evidence for the acquisition of T cell markers in the absence of the thymic microenvironment in man.

The nature of the T colony-forming cell (T-CFC) in agar is still controversial. We present evidence that blood mononuclear cells depleted of T cells by E-rosetting or lysis with OKT 3 and complement can give rise to E+ OKT 3+ colonies in the presence of supernatants of PHA-stimulated lymphocytes (P-SUP) containing a cell growth factor. Both OKT 4+ (67%) and OKT 8+ (32%) cells were found in the colonies, and less than 10% of these cells were Ia+. We consider that colonies in agar can arise from the proliferation and maturation of a circulating immature progenitor (T colony-forming cell, or T-CFC) that does not need the thymic environment to acquire the OKT 3, 4, and 8 antigens or E receptor. In contrast, Ia+ OKT 3+ cells that are maintained by P-SUP in long-term liquid culture are reportedly derived from mature T cells, and this proliferation might represent the counterpart of the in vivo response to any mitogenic stimulation of the peripheral compartment of mature T cells.

Antibodies↗
PubMed1981

Existence of a pool of T-lymphocyte colony-forming cells (T-CFC) in human bone marrow and their place in the differentiation of the T-lymphocyte lineage.

The existence and characteristics of bone marrow T-cell progenitors have not yet been established in man. Several pieces of evidence such as the reconstitution of certain immunodeficiencies by bone marrow graft suggest that T-cell precursors are present in the bone marrow. We report the growth of T-cell colonies from bone marrow populations using PHA-stimulated lymphocyte-conditioned medium containing T-cell growth factor (TCGF). Rosetting experiments and complement-dependent cytotoxicity assays with monoclonal antibodies indicate that the bone marrow T colony-forming cells (T-CFC) are E- OKT 3- and la+, i.e., immature progenitors. The colonies derived from these cells have the phenotype of mature T cells: E + OKT 3 + la- with either helper (OKT 4+) and suppressor (OKT 8 +) antigens. These results suggest that a thymic microenvironment may not be necessary for the in vitro proliferation and differentiation of the T-cell lineage in adult humans. These methodologies may permit direct investigation of early phenomena concerning the T-cell lineage, such as the acquisition of self-tolerance, the formation of a repertoire of specificities, and the HLA restriction phenomena that we believe takes place before the thymic maturation.

Animals↗
PubMed1979

Trochanter bone marrow: a source of normal human colony forming cells.

In vitro studies of human hemopoiesis are often limited by the availability of normal bone marrow. We have overcome this difficulty by taking advantage of the bone marrow fragments removed during total hip replacement. We report here a comparative study of the colony forming capacity of trochanter and sternal or iliac crest marrow from five hematologically normal donors. Our data indicate that trochanter marrow is a reliable source of normal in vitro granulocyte/macrophage colony forming cells.

Bone Marrow Cells↗