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Biomedical subjects

M A Bach

Publications and source records attributed to M A Bach.

At least 91 records · Page 5Linked to original sources

Phosphorylcholine on isologous red blood cells induces polyclonal but not anti-phosphorylcholine plaque-forming cells in mice.

It has been demonstrated in the preceding report (Bach, M. A., Beckmann, E. and Levitt, D., Eur. J. Immunol. 1984. 14: 589) that phosphorylcholine (PC) on the bacterium Streptococcus pneumoniae R36a stimulated polyclonal as well as anti-PC plaque-forming cells (PFC) in mouse spleen in vivo. In this study, red blood cells from BALB/c mice (MRBC) were either conjugated with PC, 2,4,6-trinitrophenyl (TNP) or treated with phospholipase A2 (PLA2) to expose PC on the cell membrane (determined by hemagglutination with the anti-PC myeloma HOPC8). When BALB/c mice were immunized i.v. with the conjugated or enzyme-treated MRBC, a significant polyclonal antibody response occurred (p less than 0.05) using PC-MRBC or PLA2-treated MRBC, but not with TNP-MRBC or sham-treated MRBC. No anti-PC or anti-MRBC immunoglobulin-secreting cells developed after immunization. Repeated immunization with PC-MRBC resulted in similar levels of protein A PFC after each immunization but no anti-PC, anti-MRBC or anti-PC-MRBC PFC. Thus, PC on R36a or isologous RBC stimulated increased numbers of splenic plaque-forming cells. In the case of R36a, 10-25% of these PFC produced antibodies directed towards PC. In contrast, PC-MRBC or PLA2-treated MRBC, failed to evoke any anti-PC antibody responses.

Animals↗

T-cell subsets in multiple sclerosis: a comparative study between cell surface antigens and function.

Pokeweed mitogen (PWM)-driven immunoglobulin synthesis (IgG, IgA, IgM) and concanavalin A (Con A)-stimulated suppression of allogeneic mixed leukocyte reaction (MLR) were studied and compared to T-cell subsets defined by monoclonal antibodies OKT4 and OKT8 in patients with multiple sclerosis (MS). The group of patients with active progressive MS showed diminished suppressor activity as measured by T-cell functional tests and also an elevated OKT4/OKT8 ratio. The group of MS patients in remission did not show these abnormalities. However, this correlation between functional tests and T-cell phenotypes was not found when separate individuals were considered within the subgroups of MS. Since neither OKT4 nor OKT8-reactive cells represent homogeneous functional subsets of T cells, the OKT4/OKT8 ratio does not account for the functional immunological status of separate individuals but rather provides a global evaluation of T-cell subset disturbances in different groups of diseases.

Adult↗

Influence of dose and route of Mycobacterium lepraemurium inoculation on the production of interleukin 1 and interleukin 2 in C57BL/6 mice.

Groups of C57BL/6 mice were infected either intravenously or subcutaneously with 10(5) or 10(8) Mycobacterium lepraemurium cells, and the ability of their splenic macrophages and T-cells to produce, respectively, interleukin 1 on lipopolysaccharide stimulation and interleukin 2 on concanavalin A stimulation was assessed during the course of infection. In all groups of infected mice, interleukin 1 production remained unaffected during the entire observation period, whereas interleukin 2 activity decreased as the infection progressed. Heavily infected mice (10(8) M. lepraemurium cells) showed an earlier and stronger deficiency interleukin 2 production by concanavalin A-stimulated spleen cells than did mice infected with a lower dose (10(5) bacilli), without detectable influence by the route of inoculation. In mice receiving 10(5) bacilli, minor differences were seen according to the route of infection, with a slight delay in interleukin 2 decrease in mice injected intravenously. In subcutaneously inoculated mice, the failure of spleen cells to produce interleukin 2 after concanavalin A stimulation did not correlate with the number of bacilli developing in the spleen, suggesting the existence of suppressor mechanisms acting at a distance from the site of inoculation.

Animals↗

The cellular content of dermal leprous granulomas: an immuno-histological approach.

An indirect immunofluorescence technique with monoclonal antibodies has been used to identify T cells, T helper cells, T suppressor cells, and granulocytes in the dermal granulomas of 22 patients with leprosy. In tuberculoid leprosy, T helper cells predominated and T suppressor cells were located at the periphery of well-circumscribed granulomas. In lepromatous leprosy, the two subsets of T cells were numerous in treated patients. In ENL lesions, T cells were more numerous and T helper cells predominated. Enumerations of the T cell subsets in the dermis and in the blood showed similar changes, but these changes were quantitatively more marked in the dermal granulomas.

Adolescent↗

Reactivity of histiocytosis X cells with monoclonal antibodies.

Histiocytosis X cells were demonstrated to react with T6 antigen as well as with the M1 and I1 markers of monocytes using immuno-electron microscopy and double labeling immunofluorescence technique. The data confirm the close relationship existing between histiocytic X cells, Langerhans cells and dendritic cells, and suggest to consider the T6 antigen either as an early differentiation marker of thymocytes or as a functional marker of Mononuclear Phagocyte System subpopulations.

Antibodies, Monoclonal↗

Expression of OKT 8 antigen and Fc gamma receptors by suppressor cells mediating specific unresponsiveness between recipient and donor in renal-allograft-tolerant patients.

Renal allograft tolerant patients show specific unresponsiveness in mixed-lymphocyte culture assays when confronted with donor stimulating cells. Separation of posttransplant peripheral blood lymphocytes into Fc gamma + and Fc gamma - by rosetting and into OKT8+, OKT8- by cytofluorometry enabled the demonstration of normal responses by Fc gamma - and OKT8- cells, whereas the proliferation of OKT8+ and Fc gamma + cells was depressed specifically in the presence of donor cells. Using mixing experiments, we showed that OKT8+ and Fc gamma + posttransplant lymphocytes exert a suppressive effect specific to the donor-recipient pair on the proliferative response of the pretransplant lymphocytes.

Adult↗

Deficit of interleukin 2 production associated with impaired T-cell proliferative responses in Mycobacterium lepraemurium infection.

C57BL/6 and BALB/c mice were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). At various times after infection, spleen cells were tested for their capacity to proliferate in vitro in response to concanavalin A (ConA) and to allogeneic cells. The generation of alloreactive cytotoxic T lymphocytes was also studied. The mitogen- and allogeneic-cell-induced blastogenesis of splenocytes from MLM-infected C57BL/6 and BALB/c mice was shown to be depressed during infection. The maximal decrease occurred 6 months after infection. Conversely, no reduction in the ability to generate alloreactive cytotoxic T lymphocytes was observed even after 6 months of infection. At the same time, interleukin 2 (IL2) activity generated by ConA stimulation of infected splenocytes was measured in both strains. IL2 activity in the ConA-stimulated culture supernatants was decreased as early as 1 month after MLM inoculation as compared with supernatants from age-matched control mice. Thus, IL2 production by infected-mouse spleen cells was shown to decline earlier than their proliferative responses to ConA and to allogeneic cells. ConA-induced T-cell blasts from infected mice showed a reduced ability to proliferate when incubated with an IL2-containing reference supernatant from ConA-stimulated normal spleen cells. These data suggest that a defect in IL2 production and utilization might contribute to the impairment of T cell-mediated immunity observed in MLM-infected mice.

Animals↗

[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↗

Surface Lyt phenotype of suppressor cells in C57BL/6 mice infected with Mycobacterium lepraemurium.

C57BL/6 were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). At increasing time intervals after infection different isolated splenic cell subpopulations were tested for their ability to suppress the mixed lymphocyte reaction (MLR) of normal syngeneic mouse splenocytes. During the first 6 months after infection neither T depleted nor plastic adherent spleen cells from infected mice exerted a suppressive activity on the normal mouse allogeneic proliferative response. Conversely, splenic T cells from MLM infected mice exhibited suppressive activity as early as 2 months after infection. Attempts to characterize the Lyt phenotype of splenic suppressor T cells from 6 months infected mice showed that both Lyt 1+ 2- and Lyt 2+ enriched cell subsets possessed the ability to suppress the MLR of the normal mouse spleen cells and Lyt 1+ 2- T cells were shown to be more efficient suppressors than Lyt 2+ cells.

Animals↗

In vitro proliferative response to M. leprae and PPD of isolated T cell subsets from leprosy patients.

In vitro proliferative response to Mycobacterium leprae and PPD to T cell subsets, isolated by selective depletion procedure from peripheral blood using OKT4 or OKT8 monoclonal antibodies plus complement, was investigated in leprosy patients. Whole peripheral blood mononuclear cells (PBMC) developed a strong proliferative response to both M. leprae and PPD in most tuberculoid patients. This proliferation was confined to T cells, and concerned predominantly OKT4+ cells. Both antigens, however, induced a smaller, but significant proliferation oF OKT8+ cells. In lepromatous patients, proliferative response of whole PBMC incubated with M. leprae was in most cases unsignificant, at variance with PPD-induced proliferation, which was not significantly lower than that of PBMC from tuberculoid patients. In a majority of M. leprae non-responders, neither OKT4+ nor OKT8+ enriched PBMC developed a proliferative response to M. leprae. Unexpectedly in four M. leprae unreactive patients, control treatment of PBMC with complement alone restored a strong proliferative response to M. leprae. Taken together, these results suggest that in vitro unresponsiveness to M. leprae results at least in some patients, from an active suppressor mechanism but that the effector phase of such suppression does not directly involve OKT8+ T cells.

Adolescent↗

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↗

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↗

Binding of phosphorylcholine by non-immunoglobulin molecules on mouse B cells.

Phosphorylcholine (PC), a molecule found in the cell wall of most serotypes of pneumococcus, has been used extensively as a probe for the study of network interactions during immune responses. The frequency of B lymphocytes capable of interacting with PC has not been directly examined. We used immunofluorescence to study the binding of PC and monoclonal anti-TEPC15 anti-idiotopic antibodies to murine lymphocytes. In addition to identifying PC-specific Ig molecules, PC was bound by a non-Ig molecule on the surface of a relatively large subset of B cells; this non-Ig marker shared an idiotypic determinant with the PC-binding myeloma protein HOPC8 (H8). PC-bearing R36a pneumococci bind to a similar subset of lymphocytes. This binding is inhibited specifically by PC coupled to bovine serum albumin and also by a monoclonal anti-H8 antibody. We suggest that bacterial interaction with B cells through non-Ig molecules capable of binding a dominant antigen like PC may possess functional significance, possibly during the events that lead to antibody induction by these microorganisms.

Animals↗

Tumor cell line characterization of a malignant histiocytosis transplanted into nude mice.

The successful transplantation of a human malignant histiocytosis into nude mice allowed the examination of its atypical histiocytic cell proliferation. Histiocytic type cells were identified by positive reactions with acid phosphatase and non-specific esterase and with anti human DR or OKI1 antisera. Presence of OKT9 antigen and negative results obtained with most OKT antisera, rosettes, erythrophagocytosis and lysozyme corroborate the histiocytic immature state of the cells and preclude another type of tumor. All positive tests to prove a mature mononuclear phagocytic origin were attributable to the murine host cell reaction.

Animals↗

Regulatory T cell-subset imbalance in chronic active hepatitis.

Three monoclonal anti-T-cell antibodies, specifically directed against total T cells (OKT3), inducer-helper T cells (OKT4) and suppressor/cytotoxic T cells (OKT8), were used in this study to analyze peripheral T-cell subsets in hepatitis B surface antigen (HBsAg)-positive and -negative chronic active hepatitis (CAH) patients. Results showed that a clear-cut difference exists in the distribution of peripheral T cells of these two groups of subjects. HBsAg-positive CAH patients had a numerical predominance of peripheral T lymphocytes expressing the characteristics of cytotoxic/suppressor T cells. In contrast, patients with "autoimmune" HBsAg-negative CAH exhibit a predominance of OKT4 cells, namely, the helper-inducer T-cell subset. In addition, high numbers of circulating double labeled cells (expressing both the OKT4 and the OKT8 xenoantigens) were detected in some of the HBsAg-positive and HBsAg-negative CAH patients studied.

Adult↗