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I Bartok

Publications and source records attributed to I Bartok.

7 recordsLinked to original sources
PubMed2000

Activated murine endothelial cells have reduced immunogenicity for CD8+ T cells: a mechanism of immunoregulation?

The immunogenic properties of primary cultures of murine lung microvascular endothelial cells (EC) were analyzed. Resting endothelial cells were found to constitutively express low levels of MHC class I and CD80 molecules. IFN-gamma treatment of EC resulted in a marked up-regulation of MHC class I, but no change was observed in the level of CD80 expression. No CD86 molecules were detectable under either condition. The ability of peptide-pulsed EC to induce the proliferation of either the HY-specific, H2-K(k)-restricted CD8(+) T cell clone (C6) or C6 TCR-transgenic naive CD8(+) T cells was analyzed. Resting T cells were stimulated to divide by quiescent peptide-prepulsed EC, while peptide-pulsed, cytokine-activated EC lost the ability to induce T cell division. Furthermore, Ag presentation by cytokine-activated EC induced CD8(+) T cell hyporesponsiveness. The immunogenicity of activated EC could be restored by adding nonsaturating concentrations of anti-H2-K(k) Ab in the presence of an optimal concentration of cognate peptide. This is consistent with the suggestion that the ratio of TCR engagement to costimulation determines the outcome of T cell recognition. In contrast, activated peptide-pulsed EC were killed more efficiently by fully differentiated effector CD8(+) T cells. Finally, evidence is provided that Ag recognition of EC can profoundly affect the transendothelial migration of CD8(+) T cells. Taken together, these results suggest that EC immunogenicity is regulated in a manner that contributes to peripheral tolerance.

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PubMed1999

Critical role of costimulation in the activation of naive antigen-specific TCR transgenic CD8+ T cells in vitro.

The influence of costimulation on the activation of naive CD8+ T cells and thymocytes was studied in vitro using H-Y-specific TCR-transgenic mice and H-Y antigenic peptide. Using a variety of physiological APC types, the activation of naive CD8+ T cells depended strictly on costimulation, which could not be substituted by high epitope density. T cell activation is known to be regulated by the interactions between CD86/CD80 and CD28/CD152, although it remains unclear whether the B7 isoforms have distinct roles. Addition of soluble anti-CD86 Ab led to profound inhibition of T cell reactivity, further confirming the importance of costimulation in naive CD8+ T cell activation. Finally, TCR engagement in the absence of costimulation had no effect on the subsequent reactivity of peripheral naive transgenic CD8+ T cells, but induced nonresponsiveness in mature CD8+ transgenic thymocytes. Collectively, these results demonstrate the importance of costimulation for naive CD8+ T cell activation, suggest that CD80 and CD86 can mediate opposing effects, possibly due to differential interaction with CD152 and CD28, and indicate differences in the sensitivity of immature vs mature CD8+ T cells to the induction of nonresponsiveness following costimulation-deficient Ag presentation.

Abatacept↗
PubMed1999

Anergic T cells act as suppressor cells in vitro and in vivo.

The potential suppressive effects of allospecific anergic T cells were investigated both in vitro and in vivo. Allospecific T cells were rendered unresponsive in vitro using immobilized anti-CD3 mAb. These anergic T cells profoundly inhibited proliferation of responsive T cells in an antigen-specific manner. The observed inhibition did not appear to be due to the release of inhibitory cytokines in that secretion of IL-2, IFN-gamma, IL-4, IL-10 and TGF-beta was greatly reduced following the induction of anergy, and neutralizing mAb specific for IL-4, IL-10 and TGF-beta failed to reverse the inhibition. Furthermore, the suppression mediated by anergic T cells required cell to cell contact. In vivo, adoptive transfer of anergic T cells into recipients of allogeneic skin grafts led to prolonged skin graft survival. Consistent with the lack of inhibitory cytokine production by the anergic cells, prolongation of skin allograft rejection was not influenced by the simultaneous administration of a neutralizing anti-IL-4 antibody. These results indicate that anergic T cells can function as antigen-specific suppressor cells both in vitro and in vivo.

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PubMed1998

T:T antigen presentation by activated murine CD8+ T cells induces anergy and apoptosis.

Using an IL-2-secreting, noncytolytic, H-Y-specific, CD8+ T cell clone, the functional consequences of Ag presentation by T cells to T cells were investigated. Incubation of the T cells with H-Y-soluble peptide led to nonresponsiveness to Ag rechallenge. This was due to the simultaneous induction of apoptosis, involving approximately 40% of the T cells, and of anergy in the surviving cells. These effects were strictly dependent upon bidirectional T:T presentation, in that exposure of C6 cells to peptide-pulsed T cells from the same clone induced proliferation but not apoptosis or anergy. The inhibitory effects of T:T presentation were not due to a lack of costimulation, since the T cells expressed levels of CD80 and CD86 higher than those detected on cultured dendritic cells and equipped them to function as efficient APCs for primary CD8+ T cell responses. Following incubation with soluble peptide, CD80 expression increased, and high levels of CTLA-4 (CD152) expression were induced. Although addition of anti-CTLA-4 Ab augmented proliferation in response to soluble peptide, no protection from apoptosis or anergy was observed. Neither Fas nor TNF-alpha was expressed/produced by the C6 cells, and coligation of MHC class I molecules and TCR failed to reproduce the effects of T:T presentation. Taken together, these data suggest that T:T Ag presentation induces anergy and apoptosis in murine CD8+ T cells and may reflect the regulatory consequences of T:T interactions in the course of clonal expansion in vivo.

Abatacept↗
PubMed1996

The molecular basis of hereditary complement factor I deficiency.

The molecular basis of hereditary complement factor I deficiency is described in two pedigrees. In one pedigree, there were two factor I-deficient siblings, one of whom was asymptomatic and the other suffered from recurrent pyogenic infections. Their factor I mRNA was analyzed by reverse transcription of fibroblast RNA followed by amplification using the polymerase chain reaction. Both siblings were homozygous for the same transversion (adenine to thymine) at nucleotide 1282 in the cDNA. This mutation causes histidine-400 to be replaced by leucine. The altered histidine is a semi-conserved residue within the serine proteinase family, although no function has been ascribed to it. The proband of the second pedigree studied was found to be a compound heterozygote. One allele had the same mutation as the first family, the second allele had a donor splice site mutation that resulted in the deletion of the mRNA encoded in the fifth exon (a low-density lipoprotein receptor domain) from its transcript.

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PubMed1984

Cell production and morphological pattern formation in primary brain cell cultures. I. Pattern formation within the basal layer(s).

Spontaneous pattern formation within the basal cellular layer of primary brain cell cultures were studied. Basal cells were found to be organized into a limited number of morphologically well distinguishable types of cell-arrangements. Phase contrast microscopy was used to characterize the different cell-assemblies morphologically. Under standard culture conditions the time of appearance and specific changes of relative frequency in time were also characteristic of different patterns. The distribution of mitotically active cells among the different morphological patterns within the basal layer was also investigated by recording [3H]thymidine uptake of cells. Reduction of mitotic activities of cells in the basal layer was found in the vicinity of overlying cells. In a given area of cultures the reduction of mitotic activity was proportional to the number of overlying cells. The influence of cell proliferation on the morphological pattern formation in primary cultures is discussed.

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