Target cell induced activation of NK cells in vitro: cytokine production and enhancement of cytotoxic function
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Janus kinase 3
Lymphokine-activated killer cell
NK-92
CD49b
Interleukin 3
We have demonstrated augmentation of the CD3−CD56+ natural killer (NK) and CD8+CD56− T-cell–mediated tumor cell cytotoxicity by neem leaf glycoprotein (NLGP). These NK and T cells were isolated from the peripheral blood of head and neck squamous cell carcinoma patients with a state of immunosuppression. NLGP induces TCRαβ-associated cytotoxic T lymphocyte (CTL) reaction to kill oral cancer (KB) cells. This CTL reaction is assisted by NLGP-mediated up-regulation of CD28 on T cells and HLA-ABC, CD80/86 on monocytes. CTL-mediated killing of KB cells and NK-cell–mediated killing of K562 (erythroleukemic) cells are associated with activation of these cells by NLGP. This activation is evidenced by increased expression of early activation marker CD69 with altered expression of CD45RO/CD45RA. NLGP is a strong inducer of IFNγ from both T and NK cells; however, IFNγ regulates the T-cell–mediated cytotoxicity only without affecting NK-cell–mediated one. Reason of this differential regulation may lie within up-regulated expression of IFNγ-receptor on T-cell surface, not on NK cells. This NLGP-induced cytotoxicity is dependent on up-regulated perforin/granzyme B expression in killer cells, which is again IFNγ dependent in T cells and independent in NK cells. Although, FasL expression is increased by NLGP, it may not be truly linked with the cytotoxic functions, as brefeldin A could not block such NLGP-mediated cytotoxicity, like, concanamycin A, a perforin inhibitor. On the basis of these results, we conclude that NLGP might be effective to recover the suppressed cytotoxic functions of NK and T cells from head and neck squamous cell carcinoma patients.
Granzyme
CD49b
Lymphokine-activated killer cell
CD80
Janus kinase 3
CTL*
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Abstract Activated NK T cells are known to rapidly stimulate NK cells and, subsequently, CD8+ T cells and B cells. In this report, we first demonstrate that the downstream effects induced by α-galactosylceramide activated NK T cells on NK cells are mainly dependent on IFN-γ. We found that NK T cell activation of NK cells requires a functional IFN-γ signaling in macrophages and dendritic cells but not in B cells, NK cells, or NK T cells. NK T cell activation is dendritic cell-dependent whereas NK T cell activation of NK cells is indirect and in part mediated by macrophages. Interestingly, in this context, macrophage participation in the CD1d Ag presentation of α-galactosylceramide to NK T cells is not necessary. These data indicate that NK T cell-dependent activation of macrophages is required for optimal NK T cell-induced stimulation of NK cells.
Janus kinase 3
Myeloid-derived Suppressor Cell
Lymphokine-activated killer cell
NK-92
CD49b
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Lymphokine-activated killer cell
NK-92
Interleukin 3
Janus kinase 3
Interleukin 15
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Lymphokine-activated killer cell
NK-92
Interleukin 3
Janus kinase 3
Interleukin 15
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NK-92
NKG2D
Lymphokine-activated killer cell
Janus kinase 3
Granzyme
Cancer Immunotherapy
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Janus kinase 3
Lymphokine-activated killer cell
NK-92
CD49b
Interleukin 3
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Summary We investigated the function of CD56 + CD8 + T cells (CD56 + T cells) and CD56 − CD57 + CD8 + T cells (CD57 + T cells; natural killer (NK)‐type T cells) and compared them with those of normal CD56 − CD57 − CD8 + T cells (CD8 + T cells) and CD56 + NK cells from healthy volunteers. After the stimulation with immobilized anti‐CD3 antibodies, both NK‐type T cells produced much larger amounts of interferon‐γ (IFN‐γ) than CD8 + T cells. Both NK‐type T cells also acquired a more potent cytotoxicity against NK‐sensitive K562 cells than CD8 + T cells while only CD56 + T cells showed a potent cytotoxicity against NK‐resistant Raji cells. After the stimulation with a combination of interleukin (IL)‐2, IL‐12 and IL‐15, the IFN‐γ amounts produced were NK cells ≥ CD56 + T cells ≥ CD57 + T cells > CD8 + T cells. The cytotoxicities against K562 cells were NK cells > CD56 + T cells ≥ CD57 + T cells > CD8 + T cells while cytotoxicities against Raji cells were CD56 + T cells > CD57 + T cells ≥ CD8 + T cells ≥ NK cells. However, the CD3‐stimulated proliferation of both NK‐type T cells was smaller than that of CD8 + T cells partly because NK‐type T cells were susceptible to apoptosis. In addition to NK cells, NK‐type T cells but not CD8 + T cells stimulated with cytokines, expressed cytoplasmic perforin and granzyme B. Furthermore, CD3‐stimulated IFN‐γ production from peripheral blood mononuclear cells (PBMC) correlated with the proportions of CD57 + T cells in PBMC from donors. Our findings suggest that NK‐type T cells play an important role in the T helper 1 responses and the immunological changes associated with ageing.
Interleukin 3
Janus kinase 3
Lymphokine-activated killer cell
CD49b
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K562 cells
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CD8 + T cells kill pancreatic β‐cells in a cell–cell contact‐dependent mechanism in the non‐obese diabetic mouse. CD4 + T lymphocytes are also able to kill pancreatic β‐cells, but they do not directly contact β‐cells and may use another cell type as the actual cytotoxic cell. Natural killer (NK) cells could have this role but it is uncertain whether they are cytotoxic towards β‐cells. Therefore, the requirement for NK cells in β‐cell destruction in the CD4‐dependent T‐cell antigen receptor transgenic NOD4.1 mice was examined. NK cells failed to kill β‐cells in vitro , even in the absence of major histocompatibility complex class I. We observed only 9.7±1.1% of islet infiltrating NK cells from NOD4.1 mice expressing the degranulation marker CD107a. Diabetogenic CD4 + T cells transferred disease to NOD scid .IL2Rγ −/− mice lacking NK cells, indicating that NK cells do not contribute to β‐cell death in vitro or in vivo . However, depletion of NK cells reduced diabetes incidence in NOD4.1 mice, suggesting that NK cells may help to maintain the right environment for cytotoxicity of effector cells.
Lymphokine-activated killer cell
Janus kinase 3
NK-92
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Janus kinase 3
NK-92
Lymphokine-activated killer cell
CD49b
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We investigated the individual CD8+ populations with natural killer (NK) cell markers (NK-type T cell); CD56 single positive (CD56)-T cells, CD56/CD57 double positive (DP)-T cells and CD57 single positive (CD57)-T cells in the peripheral blood. All NK-type T-cell populations expressed CD122 and intermediate levels of T-cell receptor (TCR; regular CD8+ T cells are CD122- and express high levels of TCR). The number of both DP-T cells and CD57-T cells, but not CD56-T cells, gradually increased with age. All NK-type T-cell populations produced larger amounts of interferon-gamma than did regular CD8+ T cells after stimulation with interleukin (IL)-2, IL-12 and IL-15. However, CD56-T cells and CD57-T cells but not DP-T cells showed a potent antitumour cytotoxity to NK-sensitive K562 cells, whereas only CD56-T cells showed a potent cytotoxity to NK-resistant Raji cells. Furthermore, although NK-type T cells produced large amounts of soluble Fas-ligands, their cytotoxic activities appeared to be mediated by the perforin/granzyme pathway. The oligoclonal or pauciclonal expansions of certain VbetaT cells were found in each NK-type T-cell population. The non-variant CDR3 region(s) for the TCRbeta chain(s) showed CD57-T cells and CD56-T cells to be derived from distinct origins, while the DP-T cell population consisted of a mixture of the clones seen in both CD56-T cells and CD57-T cells. Our results suggest that CD57-T cells and CD56-T cells are functionally and ontogenically different populations while DP-T cells appear to originate from both CD56-T cells and CD57-T cells.
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Lymphokine-activated killer cell
CD49b
Granzyme A
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