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Biomedical subjects

G Zlabinger

Publications and source records attributed to G Zlabinger.

12 recordsLinked to original sources

Induction of hyporesponsiveness and impaired T lymphocyte activation by the CD31 receptor:ligand pathway in T cells.

CD31 is a member of the Ig superfamily expressed on various cell types of the vasculature, including a certain subpopulation of T lymphocytes. Previous reports suggest that interaction of CD31 with its heterophilic ligand on T cells (T cell CD31 ligand) plays a regulatory role in T lymphocyte activation. Here we demonstrate that a soluble rCD31-receptorglobulin (CD31Rg) specifically down-regulated the proliferation of human peripheral blood CD31(-) T lymphocytes stimulated via CD3 and CD28 mAbs. Notably, engagement of the T cell CD31 ligand by CD31Rg during primary stimulation also induced a prolonged unresponsive state in T cells. Retroviral transduction of CD31 into CD31(-) Th clones resulted in a significant inhibition of their proliferative capacity. When cocultured with purified CD31(-) T lymphocytes, irradiated CD31-transduced Th clones counterregulated the CD3/CD28-mediated activation of these cells. Furthermore, primary stimulation in the presence of CD31-transduced Th clones induced a comparable state of hyporesponsiveness in the T cell responders as the soluble CD31Rg. Thus, by counterregulating the activation of cognate T lymphocytes, CD31-expressing T cells might contribute to the establishment and maintenance of peripheral tolerance.

Abatacept↗

Human major group rhinoviruses downmodulate the accessory function of monocytes by inducing IL-10.

Human rhinoviruses (HRVs) are the predominant cause of the common cold. Although this disease is per se rather harmless, HRV infection is considered to set the stage for more dangerous pathogens in vivo. Here we demonstrate that HRV-14, a member of the major group HRV family, can efficiently inhibit antigen-induced T-cell proliferation and T-cell responses to allogeneic monocytes. HRV-14 triggered a significant downregulation of MHC class II molecules on monocytes. Moreover, supernatants from monocytes cultured in the presence of HRV-14 strongly reduced the allogeneic T-cell stimulatory property of untreated monocytes and monocyte-derived dendritic cells (md-DCs), whereas Epstein Barr virus-transformed B-lymphoblastoid cells were not sensitive. Analysis of the supernatant revealed that HRV-14 induced the production of significant amounts of the immunosuppressive cytokine IL-10. The important T-cell stimulatory cytokine IL-12 or the proinflammatory cytokines IL-1beta or TNF-alpha were not detected or were only minimally detected. Finally, monocytes pretreated with HRV-14 were greatly inhibited in their production of IL-12 upon stimulation with IFN-gamma/LPS. These observations suggest that altered cytokine production in mononuclear phagocytes upon interaction with HRV downmodulates appropriate immune responses during the viral infection.

Antigens, CD↗

Assessing interactions of binary time-dependent covariates with time in cox proportional hazards regression models using cubic spline functions.

The Cox proportional hazards model is the most popular model for the analysis of survival data. Time-dependent covariates can be included in a straightforward manner. In most cases such covariates will be binary, indicating some form of changing group membership, with individuals starting in group 0, and changing into group 1 after the occurrence of a specific event. If there is evidence that the hazard ratio between these two groups depends on the sojourn time in group 1, then the use of cubic spline functions will allow investigation of the shape of the supposed effect and provide two main advantages-no particular functional form has to be specified and standard computer software packages like SAS or BMDP can be used.

Clinical Trials as Topic↗

Influence of human leukocyte antigen matching on long-term outcome after lung transplantation.

BACKGROUND AND METHODS: The importance of human leukocyte antigen matching for long-term outcome after lung transplantation is uncertain. We therefore analyzed retrospectively 78 consecutive primary, isolated lung transplantations (37 female, 41 male; 40 single, 38 bilateral) performed between October 1989 and October 1995 for which human leukocyte antigen typing of both donor and recipient was available. The follow-up ranged from 1 day to 60.3 months. Graft failure, defined as retransplantation or patient death, served as end point. RESULTS: Graft survival was significantly better with one mismatch at the B locus than with two mismatches (p = 0.046): 67% versus 51% and 61% versus 25% graft survival at 12 and 36 months, respectively. For the B and DR loci combined, a marked matching effect was also observed (p = 0.21 for zero to two mismatches versus three to four mismatches: 81% versus 62% and 51% versus 29% graft survival at 12 and 36 months, respectively. The sum of mismatches at the A, B, C, and DR loci combined showed a similar effect (p = 0.17 for zero to four mismatches versus five to eight mismatches: 83% versus 62% and 58% versus 29% graft survival at 12 and 36 months, respectively. Although no clear effect could be shown for the isolated DR locus, the outcome for the three patients with zero mismatches was notably good: one patient is alive at 27 months, two died 37 and 48 months after transplantation. The number of acute rejection episodes showed a clear but insignificant correlation to the number of mismatches. A similar trend was observed for the incidence of bronchiolitis obliterans syndrome. CONCLUSIONS: In summary, a strong influence of human leukocyte antigen matching on the long-term outcome after lung transplantation is suggested by our results. A clear trend toward improved graft survival with better human leukocyte antigen matching was observed, with the most significant effect occurring at the B locus.

Adolescent↗

Peripheral blood mononuclear cells of splenectomized patients are unable to differentiate into immunoglobulin-secreting cells after pokeweed mitogen stimulation.

The function of B cells from the peripheral blood of splenectomized patients has been investigated at the cellular level. The peripheral blood of these patients contained normal numbers of mononuclear cells (MNC) spontaneously secreting IgG and IgM, but an increased amount of IgA-secreting cells. In contrast to MNC isolated from healthy controls, the patients' peripheral blood MNC were unable to differentiate into immunoglobulin-secreting cells in a pokeweed mitogen-driven culture system. Proliferation in response to pokeweed mitogen, however, was significantly higher with patient MNC as compared to control MNC.

Adolescent↗

Plaque-forming cells in human cord blood: a soluble factor suppressing differentiation but not proliferation of B cells.

Cord blood-derived T cells have been shown to suppress differentiation of B cells into immunoglobulin-secreting cells and proliferation of mononuclear cells (MNC). We report about a soluble factor present in the supernatant of pokeweed mitogen (PWM)-stimulated cord blood MNC which was able to suppress significantly the number of plaque-forming cells (PFC) in adult MNC populations, but had no effect upon proliferation of adult MNC in response to PWM and allogeneic MNC. The number of PFC was not suppressed by supernatant from unstimulated cord blood MNC or by PWM-stimulated adult MNC.

Antibody-Producing Cells↗

[IgA rheumatoid factors in ankylosing spondylitis].

151 cases of ankylosing spondylitis, arranged in clinical stages I-IV, were investigated by immunological methods (determination of HLA-B27, immunocomplexes: conglutinin-, Clq-assay; IgG-, IgM-, IgA-rheumatoid factors) and with regard to acute phase proteins (CRP, C3/C4, alpha 1-acid glycoprotein). IgA-rheumatoid factors were demonstrated as dependent upon the stage of the disease in 23-41% of cases and appeared in 20-23% of cases simultaneously with immunocomplexes. Immunocomplexes appeared in 20-23% of cases. With regard to investigations of acute phase proteins, sedimentation rate and CRP correlated best. The frequent appearance of IgA-rheumatoid factors allows a definition of ankylosing spondylitis as seronegative only as far as the determination of IgG- and IgM- rheumatoid factors is concerned.

Acute-Phase Proteins↗