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Biomedical subjects

R Schwinzer

Publications and source records attributed to R Schwinzer.

At least 55 records · Page 3Linked to original sources
PubMed1990

Different activation states of human lymphocytes after antibody-mediated stimulation via CD3 and the alpha/beta T-cell receptor.

BMA031 is an IgG2b antibody directed towards the human alpha/beta T-cell receptor that is able to induce proliferation of peripheral blood mononuclear cells independent of antibody crosslinking. The proliferative response to BMA031 during the first 3 days of culture is usually of similar magnitude to that induced by the IgG2a CD3 antibody OKT3 but decreases quickly afterwards. Stimulation by BMA031 induces no measurable IL-2 release, very low expression of the IL-2 receptor, and does not trigger cytotoxic effector function. However, cross-linking of the antibody or addition of IL-2 leads to enhanced and prolonged proliferation, strong IL-2 receptor expression, and cytotoxic activity, features that are usually found after stimulation by the IgG2a CD3 antibody OKT3 in soluble form. The stimulatory effect of BMA031 cannot be diminished by IL-2 receptor blocking, whereas stimulation by OKT3 is strongly reduced. Moreover, proliferation induced by BMA031 has lower sensitivity to inhibition by ciclosporin than OKT3. From these results two major conclusions can be drawn: (1) an IL-2-independent way of activation may be important for the short-term proliferation of the T cells stimulated by BMA031 and (2) after stimulation by BMA031, cells reach a state of activation that is different from that induced by OKT3. These differences are most likely related to the different specificities of the antibodies, alpha/beta TcR versus CD3, suggesting that different activation signals are triggered via CD3 and via the alpha/beta TcR.

Antibodies, Monoclonal↗
PubMed1989

Glomerular mesangial cells in local inflammation. Induction of the expression of MHC class II antigens by IFN-gamma.

Glomerular mesangial cells (MC) were isolated from rats and cultured for a prolonged period of time, resulting in a homogeneous cell population. MC were characterized as belonging to the smooth muscle type. They were negative for MHC class II expression. IFN-gamma and TNF alpha suppressed the proliferation of MC, demonstrating receptors for these cytokines on MC. IFN-gamma or TNF alpha, respectively, enhanced basal MHC class I Ag expression of proliferating cells in culture. The combination of the two cytokines yielded stronger effects. IL-1 beta was ineffective in enhancing MHC class I Ag expression, although MC possessed receptors for this cytokine. IFN-gamma dose dependently induced the expression of MHC class II Ag, while TNF alpha or IL-1 beta were ineffective alone. The combination of IFN-gamma with TNF alpha or IL-1 beta resulted in an enhanced induction of MHC class II Ag, compared to IFN-gamma administration alone. These findings suggest that proliferating mesangial cells of the smooth muscle type may participate in local inflammatory responses or substitute for macrophages by meeting the accessory cell requirement in the interaction with T lymphocytes. Furthermore, the data have important implications for the evaluation of the role of mesangial cells in autoimmune disease of the kidney.

Animals↗
PubMed1989

Cooperative effects of colony-stimulating factor 1 and recombinant interleukin 2 on proliferation and induction of cytotoxicity of macrophage precursors generated from mouse bone marrow cell cultures.

Precursor cells for NK activity, present in the light fraction of fresh mouse bone marrow, were cultivated in vitro in the presence of either CSF-1, IL-2, or a combination of both factors. In the presence of only CSF-1, strong proliferation was induced. Cells quickly passed the macrophage precursor stage and matured to typical macrophages. Neither granula formation nor NK activity were induced. Under culture conditions with only IL-2 NK activity had developed after 3 d, however, no significant proliferation occurred. In the presence of both factors strong proliferation was induced, and concomitantly, granula formation and NK activity developed. Apparently, proliferation depended on CSF-1 and granula formation, and NK cytotoxicity was induced by IL-2. When proliferating cells with strong anti-YAC-1 activity from a culture in CSF-1 plus IL-2 were further cultivated in only IL-2, the content of granula further increased, whereas proliferation gradually stopped. In contrast, when these cells from CSF-1 plus IL-2 culture were further cultivated in only CSF-1, granula disappeared and NK activity was lost, whereas sustained proliferation and differentiation to macrophages occurred. Only under culture conditions with both factors were proliferation and NK activity both maintained. More than 90% of cells from a 3-d culture in CSF-1 plus IL-2 expressed the NK 1.1. marker, whereas F4/80 was only marginally detected by FACS analysis. After two further days in culture, 70% of the cells expressed F4/80 and 60% coexpressed NK 1.1. and F4/80. By setting the size scatter in order to gate for large granular cells, a population was obtained with 100% coexpression of NK1.1. and F4/80. The data indicate that early cells of the macrophage lineage can develop into different functional and morphological directions depending on the varying influence of IL-2 and CSF-1.

Animals↗
PubMed1989

Effect of human recombinant IL-2 on murine macrophage precursors. Involvement of a receptor distinct from the p55 (Tac) protein.

Homogeneous populations of bone marrow-derived murine macrophage precursors are able to respond to human rIL-2. A prolonged exposure to the lymphokine results in proliferation and in the final differentiation of macrophage precursors to mature macrophages, as shown by follow-up of the antigenic profile by means of cytofluorograph analysis. The frequency of the IL-2-responding cells was 1/48 as determined by limiting dilution analysis, and no cell death was evidenced in soft agar cultures. An analysis of the IL-2-binding sites conducted on bone marrow-derived macrophage precursors revealed the presence of 4000 binding sites with intermediate affinity (Kd approximately 3 x 10(-9)). Bone marrow-derived macrophage precursors did not react, even after prolonged culture in IL-2-conditioned media, with mAb recognizing the binding site (AMT-13, 3C7) or a binding site-associate molecule (7D4) of a Mr 50,000 to 60,000 component of the IL-2R expressed by the IL-2-dependent T cell line CTLL-2. Cross-linking studies showed the presence of a single binding protein, with an apparent Mr of 70,000. Macrophage precursors also proved able to internalize human rIL-2 within the first 20 min of incubation at 37 degrees C. The implications of these findings are discussed.

Animals↗
PubMed1989

T cell differentiation in athymic nude rats (rnu/rnu): demonstration of a distorted T cell subset structure by flow cytometry analysis.

The expression of T cell-associated antigens was analyzed on extrathymically differentiated T cells from athymic nude (rnu/rnu) rats. Two-color flow cytometry and monoclonal antibodies were used to compare the subset structure of the rnu/rnu T cell population with that of normal T cells. In adult nude rats CD4+ and CD8+ cells were found which co-expressed the OX19 antigen (CD5) clearly defining them as T cells. Double-positive (CD4+CD8+) cells were not detected in nylon wool-enriched rnu/rnu T cells. The ratio of CD4+ to CD8+ cells in nude rat lymph node cells did not significantly differ from normal T cells. However, the composition of the nude rat CD4+ and CD8+ subsets [as identified by the subset-dividing monoclonal antibodies OX22 and P4/16 (anti-RT6)] differed from that found in control rats. The most striking observation among the rnu/rnu CD4+ subset was an inversion in the ratio of OX22+ to OX22- cells (0.5) compared to normal rats (2.3). Only 61% of the nude rat CD4+ cells were found to be RT6+ compared to 85% of rnu/+ CD4+ cells. In the rnu/rnu CD8 subset the proportion of RT6 co-expressing cells was also markedly reduced (38% vs. 77% of the CD8+ subset). Furthermore, the nude rat CD8+ subset contained a substantial number of OX22- cells which were nearly absent in normal rats. The demonstration of cells bearing T cell markers in adult athymic rats further confirms the existence of an extrathymic pathway of T cell differentiation. The unusual T cell subset composition found in athymic rats, however, indicates that T cell subset generation and/or maintenance along this pathway differs from normal T cell development.

Animals↗
PubMed1989

Cholera toxin modulates the T cell antigen receptor/CD3 complex but not the CD2 molecule and inhibits signaling via both receptor structures in the human T cell lymphoma Jurkat.

The human T cell lymphoma Jurkat can be activated by stimuli directed either against the T cell antigen receptor-CD3 antigen complex (TcR/CD3) or the CD2 molecule. Stimulation of cells via the TcR/CD3-complex or via the CD2 molecule increases inositol phosphates and cytoplasmic free calcium. Pretreatment of Jurkat cells with cholera toxin leads to a decrease of TcR/CD3 expression on the surface of the cells, while the expression of CD2 is unaffected. In contrast to this distinct effect on the receptor expression, signaling via both pathways is inhibited by cholera toxin. The most convincing explanation for the cholera toxin-mediated inhibition of signaling is that cholera toxin interrupts the signaling pathways at a point where both, stimulation via TcR/CD3 and via CD2, use the same route. The earliest common point of the two signaling pathways, at least in the Jurkat cell line, seems to be the CD3 complex because after its down-regulation (and functional inactivation) both pathways of activation are interrupted.

Antigens, Differentiation, T-Lymphocyte↗