Dendritic Cells Lose Ability to Present Protein Antigen after Stimulating Antigen-Specific T Cell Responses, despite Upregulation of MHC Class II Expression

Bernhard, Helga; Huseby, Eric S.; Hand, Susan L.; Lohmann, Matthias; Batten, Wendy Y.; Disis, Mary L.; Gralow, Julie R.; Büschenfelde, K H Meyer zum; Öhlén, Claes; Cheever, Martin A.

doi:10.1016/s0171-2985(00)80075-3

Cited by 13 publications

(6 citation statements)

References 36 publications

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“…The expression of CD86 molecules increased further during additional co-culture of DCs with allogeneic T cells. Similar observations were reported by Bernhard et al (2000). What we also showed is that the differences in the level of CD86 expression observed between DC-LPS, DC-MCM and DC-TNF at the end of the initial maturation period persisted after subsequent co-culture with T cells.…”

Section: Discussionsupporting

confidence: 91%

Late dendritic cells are still able to evoke a potent alloreactive CTL response

et al. 2008

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Section: Discussionsupporting

confidence: 91%

Late dendritic cells are still able to evoke a potent alloreactive CTL response

et al. 2008

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“…As cytokines have been shown to be closely related to the expression of the costimulatory molecules (41), we next investigated the specific effects of IL‐6 and IL‐10 on the B7 molecules. We found that in vitro IL‐6 stimulation resulted in a dose‐dependent increase in both CD80 and CD86 expression on peripheral blood APC, an effect that is not surprising in light of the wide range of stimulatory activities ascribed to IL‐6, including enhancement of dendritic cell maturation (42), in addition to T‐cell proliferation and B‐cell differentiation (27). In vitro stimulation with IL‐10 reduced the expression of both costimulatory molecules on the blood cells of these patients, also in a dose‐dependent manner, a result that is supported by previous reports that the inhibitory effect of IL‐10 on T‐cell responses may be related to costimulatory molecule expression on APC (43, 44).…”

Section: Discussionmentioning

confidence: 80%

Association of cytokine single nucleotide polymorphisms with B7 costimulatory molecules in kidney allograft recipients

Hutchings

Guay‐Woodford

Thomas

et al. 2002

Pediatric Transplantation

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African-American race is associated with an increased risk of allograft loss, suggesting that African-American patients may form an immunologically higher risk group. Previously, we demonstrated that immune cell costimulatory molecule expression is significantly higher in African-Americans than in Caucasians. Polymorphic variations in the genes for cytokines have been associated with a number of immunological conditions, and with transplant rejection. This study was performed to determine the distribution, in African-American and Caucasian renal transplant recipients, of single nucleotide polymorphisms (SNPs) in the following cytokine genes: tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-6, IL-10, and transforming growth factor-beta (TGF-beta). Cytokine production from blood cells was determined, and cell-surface B7 (CD80, CD86) expression was measured. There was a significant link between IL-10 genotype and acute rejection episodes, but only in African-American patients (p < 0.01). Also, African-American patients had a significantly higher probability of having the IL-6 G-allele (p < 0.0001), which is associated with a high production of IL-6 protein. Incubation of blood cells with IL-6 resulted in increased expression of surface CD80 and CD86, while IL-10 decreased CD80 expression. This study demonstrated a clear correlation of the IL-6 G-allele with increased cellular CD80 expression and the IL-10 G-allele with decreased CD80 expression. These data raise the possibility that specific genotypes are associated with local cytokine regulation of cell-surface costimulatory molecule expression. African-American patients may have a genetically determined, quantitatively different immune response than Caucasian patients, contributing to adverse transplant outcomes.

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“…Because activated T cells can induce maturation of DCs by enhancing surface expression of MHC and costimulatory molecules (Bernhard et al, 2000), we were specifically interested in the effects of MC-T cell interactions on the expression of MHC class I and costimulatory molecules by MCs. Therefore, unpulsed or OVA 257-264 -pulsed MCs were cocultured with CD8 + T cells for 48 hr and MCs were analyzed for surface MHC class I expression by flow cytometry.…”

Section: T Cell Responses In Vitro and In Vivomentioning

confidence: 99%

Mast Cell-Mediated Antigen Presentation Regulates CD8+ T Cell Effector Functions

et al. 2009

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The characteristics, importance, and molecular requirements for interactions between mast cells (MCs) and CD8(+) T cells have not been elucidated. Here, we demonstrated that MCs induced antigen-specific CD8(+) T cell activation and proliferation. This process required direct cell contact and MHC class I-dependent antigen cross-presentation by MCs and induced the secretion of interleukin-2, interferon-gamma, and macrophage inflammatory protein-1alpha by CD8(+) T cells. MCs regulated antigen-specific CD8(+) T cell cytotoxicity by increasing granzyme B expression and by promoting CD8(+) T cell degranulation. Because MCs also upregulated their expression of costimulatory molecules (4-1BB) and released osteopontin upon direct T cell contact, MC-T cell interactions probably are bidirectional. In vivo, adoptive transfer of antigen-pulsed MCs induced MHC class I-dependent, antigen-specific CD8(+) T cell proliferation, and MCs regulated CD8(+) T cell-specific priming in experimental autoimmune encephalomyelitis. Thus, MCs are important players in antigen-specific regulation of CD8(+) T cells.

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Dendritic Cells Lose Ability to Present Protein Antigen after Stimulating Antigen-Specific T Cell Responses, despite Upregulation of MHC Class II Expression

Cited by 13 publications

References 36 publications

Late dendritic cells are still able to evoke a potent alloreactive CTL response

Late dendritic cells are still able to evoke a potent alloreactive CTL response

Association of cytokine single nucleotide polymorphisms with B7 costimulatory molecules in kidney allograft recipients

Mast Cell-Mediated Antigen Presentation Regulates CD8+ T Cell Effector Functions

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