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Biomedical subjects

J F Bach

Publications and source records attributed to J F Bach.

At least 505 records · Page 28Linked to original sources

Effect of a synthetic thymic factor (facteur thymique serique) on natural killer cell activity in humans.

The effect of the serum thymic factor, FTS, on human NK cells was studied. NK cell activity was measured in a 51Chromium-release assay in which effector cells were peripheral blood lymphocytes (PBL) or bone marrow (BM) lymphocytes from healthy individuals and patients, and targets were K562 cells. When added in vitro in this assay, FTS modulated NK cell activity of normal PBL. Low concentrations of FTS (10(-2) ng/ml) increased NK activity (P less than 0.001) whereas higher concentrations decreased it (P less than 0.01) for 10 and 10(2) ng/ml. FTS exhibited no effect on NK cell activity of BM lymphocytes. When administered in vivo to 4 cancer patients (10 micrograms/kg i.v. every 3 days), FTS progressively increased peripheral NK activity in two patients with low pre-treatment NK values, whereas it decreased NK activity in two patients with previously normal or high NK values. The mechanism by which FTS modulates NK cell activity is still unknown but such modulation suggests that NK cells belong in part to the T-lineage.

Bone Marrow Cells↗

[Production of human antitetanus antibodies by hybridomas].

Peripheral blood lymphocytes from healthy people recently immunized against tetanus toxoid (TT) were fused with human malignant B-cell lines or mouse myeloma cells (X63 Ag8.653) in an attempt to establish stable B cell hybridomas secreting anti TT antibodies. Human-human fusion experiments were not successful. In contrast, the five heterospecific fusion experiments yielded between 60 and 100% of wells that contained growing hybrids. Five of these hybrids repeatedly secreted anti-TT antibodies. One of the hybrids was cloned and secreted 10-20 micrograms/ml of human IgM, lambda anti-TT antibody. Heterospecific hybridization thus appears as an interesting method to obtain human monoclonal antibodies, allowing the study of their properties.

Animals↗

Murine monoclonal anti-DNA antibodies with an absolute specificity for DNA have a large amount of idiotypic diversity.

The clonal heterogeneity of nine monoclonal antibodies with absolute specificities for deoxyribonucleic acid (DNA) was analyzed. These monoclonal anti-DNA antibodies were generated in three different fusion experiments using autoimmune (NZB X NZW)F1 mouse spleen cells. Isoelectric focusing analyses demonstrated different isoelectric points within the IgG2a and IgG2b subclasses. Three anti-idiotypic antisera were prepared (one in a rabbit and two in mice) against two monoclonal anti-DNA antibodies. These antisera detected idiotypic determinants uniquely associated with homologous hybridoma anti-DNA antibodies. Two of these idiotypes could be detected at low levels in the sera of (NZB X NZW)F1 mice. Anti-PME77 idiotypic antiserum had no effect in vitro on the total binding capacity of (NZB X NZW)F1 sera. Taken together these results demonstrate that, in (NZB X NZW)F1 mice, the anti-DNA antibody repertoire contains molecules that show similar antigen binding characteristics but are not structurally uniform.

Animals↗

Interest in and limitations of monoclonal anti-T-cell antibodies for the follow-up of renal transplant patients.

The OKT series of anti-T-cell monoclonals has been used on 442 occasions in 41 renal allograft recipients in a 6-12 month follow-up study. Standard immunosuppressive therapy (including antithymocyte globulin in 26 patients) tended to decrease the helper-inducer/suppressor-cytotoxic cell ratio (OKT4/OKT8). Conversely, 71% of 35 renal failure episodes were associated with increased OKT4/OKT8 ratios. Twenty-three percent of renal failure episodes were associated with dramatically decreased OKT4/OKT8 ratios. At least half of these cases could be explained by a cytomegalovirus infection. In fact, similar infections were found in 6 out of 17 patients with low OKT4/OKT8 values in the absence of renal failure. These results prompt us to use anti-T cell monoclonals for the diagnosis of rejection because only nine episodes of transient increase in the OKT4/OKT8 ratio were observed in the absence of rejection. The interest of this new method for the immunological follow-up of transplanted patients is, however, limited by the difficulty in interpreting a significant percentage of tests because of (1) the presence of doubly labeled cells (OKT4+OKT8+) or the significant discrepancy between the number of OKT3+ cells and total cells labeled with OKT4 and/or OKT8 antibodies; (2) gross lymphocytopenia--most often observed in patients receiving antithymocyte globulins plus steroids; and (3) the clinically unexplained shifts in the T cell subset ratios mentioned above.

Antibodies, Monoclonal↗

[Antigenic markers of immunocompetent cells in rheumatoid synovial membrane].

Immunologic characteristics of cells present in rheumatoid synovium from 15 patients were analyzed either "in situ" on frozen sections or after elution. Monoclonal antibodies directed against T cell subpopulation antigens and anti-Ia-like were used. T cells bearing the phenotype T3+, T4+, Ia+ are numerous, and they appeared gathered in lymphoid follicles and in perivascular areas. They are in close relationship with large Ia+ cells probably macrophagic in nature. Numerous dendritic cells as well as intimal cells are also Ia+. Some ratios T8+/T4+ cells are higher than results previously reported. This discrepancy could be related to drugs received by the patients before surgery.

Anti-Inflammatory Agents↗

Interaction of thymopoietin peptides with the specific receptor of facteur thymique serique (FTS).

The capacity of ubiquitin (UB) and thymopoietin II (TP) related peptides (TP 5 and TP 13) to interfere with the specific binding of [3H]FTS on intact 1301 cells or on 1301 plasma membrane preparations was studied. All 3 peptides significantly inhibited the binding of [3H]FTS to its receptors on intact 1301 cells at concentrations 20 to 100 times higher than FTS itself. Conversely, none of the 3 peptides provided a significant inhibition of the specific [3H]FTS binding to plasma membrane preparations of 1301 cells compared to control peptides. These contrasted results suggest that TP-related peptides and, to a lesser degree, UB may share the same target cells with FTS and interfere with FTS effects on T cells, but this interaction probably does not involve direct high affinity binding to the FTS receptors.

Animals↗

Thymic hormone containing cells. II. Evolution of cells containing the serum thymic factor (FTS or thymulin) in normal and autoimmune mice, as revealed by anti-FTS monoclonal antibodies. Relationship with Ia bearing cells.

The number of thymic epithelial cells containing the serum thymic factor (FTS or thymulin), assessed by indirect immunofluorescence using an anti-FTS monoclonal antibody, was studied in the thymus of normal and autoimmune mice as a function of age. In normal mice the number of FTS+ cells was constant until the age of 6 months and then began to decline. In autoimmune strains, the age linked decline was premature being already significant at 10 weeks of age. These findings were paralleled by the age associated decline of FTS blood levels in all strains studied. Double labelling experiments showed that in both normal and autoimmune mice, FTS+ cells were Ia negative, suggesting that these cells belong to a specific subpopulation of the thymic epithelial reticulum.

Aging↗

T cell subpopulations defined by monoclonal antibodies in autoimmune hemolytic anemia.

T cell subsets were studied using monoclonal anti-T cell antibodies in 10 patients with IgM cold agglutinins and 30 patients with IgG warm autoantibodies. Two of the 10 patients with cold agglutinin disease had abnormally low helper/suppressor T cell ratio. In the 30 patients with IgG warm autoantibodies this ratio was abnormally low in 7 and abnormally high in 7 other patients. Treatment by steroids or immunosuppressive agents tended to decrease OKT4/OKT8 ratio since high ratios were essentially found in untreated patients. This report documents the high incidence of T cell imbalance in autoimmune hemolytic anemia due to IgG warm autoantibodies and comments on its significance in the light of the great heterogeneity of this syndrome.

Adolescent↗

A murine monoclonal antibody against blood group H type-1 and -2 structures.

A murine anti-H monoclonal antibody was produced. This antibody, called sp115, is an IgM that does not agglutinate classical Bombay. Sp115 may differentiate the two categories of H-deficient phenotypes. It detects H substance in both plasma and fresh saliva. Tissue antigen is found when using this antibody. The specificity of sp115 antibody was determined by adsorption with, and elution from synthetic oligosaccharide immunoadsorbents. Sp115 does not distinguish H type-1 and H type 2-structures.

ABO Blood-Group System↗

Marked reduction of DNA antibody production and glomerulopathy in thymulin (FTS-Zn) or cyclosporin A treated (NZB X NZW) F1 mice.

In this study we have evaluated the action of two compounds, cyclosporin A (Cy A) and thymulin (FTS-Zn) in old (NZB X NZW) F1 male mice which develop severe autoimmune disease. Compared with control mice, thymulin and Cy A treated mice already showed by 2 weeks a dramatic diminution of their anti-DNA antibody level which remained low throughout the treatment period and persisted for 7 weeks afterwards. Renal specimens were studied by direct immunofluorescence in Cy A and thymulin treated mice. Glomerular deposits were decreased compared with control mice; these differences were particularly clearcut for IgG1 and IgG2 deposits. Finally, thymulin (FTS-Zn) and Cy A appeared to induce the same improvement of DNA titres and glomerulopathy in (NZB X BW) F1 mice.

Animals↗

[In vitro regulation of the secretion of thymulin (STF) by human thymic epithelial cells].

The presence of thymulin (formerly called Facteur Thymique Sérique, FTS) in cultured human thymic epithelial cells was studied using a monoclonal anti-thymulin antibody in an immunofluorescence technique. The percentage of thymulin-containing cells increases gradually as a function of time, from 10% at day 4 to 90% at day 14. Furthermore, this increase can be prevented by the addition of thymulin in the culture medium. These data suggest a feedback control of thymulin secretion by thymic epithelial cells.

Antibodies, Monoclonal↗

Thymic dysfunction in the mutant diabetic (db/db) mouse.

Thymic function has been explored in genetically diabetic homozygous C57BL/KsJ (db/db) mice by evaluating their serum thymic factor (FTS) levels with a rosette assay. As previously reported for other autoimmune mice (NZB or MRL/I mice), the age-dependent decline of FTS levels was significantly accelerated in diabetic mice when compared to heterozygous littermates. Furthermore, FTS inhibitory molecules were detected in db/db mouse sera (as early as 10 wk of age) as evaluated by their ability to absorb in vitro the activity of synthetic FTS in the rosette assay, and in vivo for their capacity to induce the disappearance of endogenous FTS when injected into normal mice. These inhibitors were shown to be immunoglobulins. Histologically, the thymus presented an accelerated involution starting with a cortical lymphocytic depletion and an increased number of Hassall's corpuscles. Ultrastructural studies showed alterations in thymic epithelial cells, mainly represented by an increasing number of cytoplasmic vacuoles. By means of indirect immunofluorescence with anti-FTS monoclonal antibodies, it was shown that the number of FTS+ cells was reduced in db/db mouse thymuses: at the age of 22 wk, diabetic mice had 10 times fewer FTS+ cells than heterozygotes of the same age. Taken together, these results indicate important abnormalities in the thymus of diabetic mice. It is possible that the associated lymphocyte dysfunction plays a role in the pathogenesis of the autoimmune disease presented by db/db mice.

Aging↗

Soluble factors for B cell activation: a T cell hybridoma that secretes a specific B cell growth factor.

A murine T cell hybridoma, T91, has been established by fusion of BALB/c Con A-activated spleen cells with BW 5147 HAT-sensitive thymoma cells. T91 constitutively produced a factor that markedly enhanced the proliferative response to LPS of B cells cultured at low cell density. This factor is nonmitogenic by itself. It maintains in the absence of LPS, the proliferation of B cell blasts previously activated with LPS for 3 days. T91 supernatant contains neither IL 1 nor IL 2 nor TRF activity, and mixing experiments indicate the absence of factors suppressing these activities. The data suggest the existence of a specific B cell growth factor compatible with a two-signal model for B lymphocyte activation.

Animals↗

Sezary syndrome. I. Specific skin-directed migration of peripheral blood lymphocytes.

The in vitro migration of peripheral blood lymphocytes (PBL) from Sezary syndrome (SS) patients and from controls was studied using a migration assay under agar. Only PBL from SS patients migrate to normal allogeneic skin. This migration is organ specific. It requires the integrity of lymphocyte membrane receptors. Serum factors are not involved. Studies of the nature of these migrating lymphocytes using monoclonal antibodies suggest that they belong to a subset of helper T cells. These data indicate a functional impairment of SS lymphocytes, which enables them to respond to a skin-derived signal.

Blood Physiological Phenomena↗

Thymic hormone containing cells. III. Evidence for a feed-back regulation of the secretion of the serum thymic factor (FTS) by thymic epithelial cells.

Cells containing the serum thymic factor (FTS), as measured by indirect immunofluorescence, were studied in mice either FTS depleted by injection of anti-FTS monoclonal antibodies or immunization against FTS coupled to bovine serum albumin (FTS-BSA), or FTS enriched by multiple injections of synthetic thymulin (FTS-Zn). Injections of thymulin did not significantly depress FTS secretion. Conversely, long term elimination of FTS from peripheral blood caused a great increase in the thymic intracellular content of FTS, as evidenced by the higher number of FTS containing cells observed with immunofluorescence. These data could provide the first evidence of a feed-back control of thymic endocrine function.

Animals↗

Study of blood group B antigen with a specific monoclonal antibody (anti-B, b-183).

A murine anti-B monoclonal antibody was obtained by the hybridoma technique. This antibody called anti-B (b-183) is of IgM nature; it is capable of agglutinating normal B, B3, Bx, cis AB and some acquired B red cells. Its association constant is 1.1 X 10(8) l/mol, and appears high compared to those of the monoclonal anti-A. This monoclonal anti-B was used to determine the number of B sites on B3 and Bx red cells.

ABO Blood-Group System↗