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https://hdl.handle.net/2440/23492
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Type: | Journal article |
Title: | Natural killer cells prime the responsiveness of autologous CD4(+) T cells to CTLA4-Ig and interleukin-10 mediated inhibition in an allogeneic dendritic cell-mixed lymphocyte reaction |
Author: | Newland, A. Russ, G. Krishnan, R. |
Citation: | Immunology, 2006; 118(2):216-223 |
Publisher: | Blackwell Publishing Ltd |
Issue Date: | 2006 |
ISSN: | 0019-2805 1365-2567 |
Abstract: | Cytotoxic T-lymphocyte antigen 4 immunoglobulin (CTLA4-Ig) and interleukin (IL)-10 are immunomodulatory molecules which target CD28 costimulation by acting either directly or indirectly on the CD80/86 receptors on dendritic cells (DCs). This study examined the effect of combined treatment with CTLA4-Ig and IL-10 on T-cell responsiveness in a dendritic cell-mixed lymphocyte reaction (DC-MLR). T cells derived from nylon wool enrichment (NWT cells) demonstrated 15% (P = 0.006) and 10% (P = 0.0015) inhibition of proliferation with suboptimal doses of IL-10 (5 ng/ml) and CTLA4-Ig (20 ng/ml), respectively. Combined treatment with both agents resulted in 38% inhibition (P = 0.004) of the MLR response compared with untreated controls. In contrast to NWT cells, which consisted of CD4+, CD8+ and CD56+ (NK) cells, purified CD4+ T cells were less responsive to immunomodulation by CTLA4-Ig and IL-10. Repletion of the CD4+ T cells with NK cells restored IL-10 and CTLA4-Ig mediated immunomodulation, suggesting a role for NK cells in the regulation of DC-T-cell interactions. The specific effect of NK cells on DC activation was demonstrated by CD80 up-regulation on DCs in the absence of T cells. However, in the absence of DCs, NK cells augmented the proliferation of autologous CD4+ T cells stimulated by anti-CD3 monoclonal antibody (mAb), which was blocked by CTLA4-Ig. It is proposed that, in the MLR, immunomodulation by suboptimal CTLA4-Ig and IL-10 is influenced by cellular interactions of NK cells with DCs and T cells involving DC lysis and costimulation. Thus, NK cells prime both DCs and T cells to low doses of CTLA4-Ig and IL-10 during alloimmune responses, providing evidence for the potential interaction between innate and adaptive immunity. |
Keywords: | costimulation cytotoxic T-lymphocyte antigen 4 dendritic cells interleukin-10 mixed lymphocyte reaction natural killer cells |
DOI: | 10.1111/j.1365-2567.2006.02359.x |
Published version: | http://dx.doi.org/10.1111/j.1365-2567.2006.02359.x |
Appears in Collections: | Aurora harvest 6 Medicine publications |
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