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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(s) -
Newland Ashley,
Russ Graeme,
Krishnan Ravi
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02359.x
Subject(s) - mixed lymphocyte reaction , prime (order theory) , biology , natural killer t cell , immunology , microbiology and biotechnology , t cell , chemistry , immune system , combinatorics , mathematics
Summary 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.