IL-10 inhibits apoptotic cell death in human T cells starved of IL-2

Taga, Kazuyuki; Cherney, Barry; Tosato, Giovanna

doi:10.1093/intimm/5.12.1599

Cited by 115 publications

(63 citation statements)

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“…These observations are reminiscent of previous studies showing that IL-10 can rescue human CD8 þ T cells from apoptotic cell death. 39,74,75 The signalling cascade activated by IL-10 differs from that used by IL-2 and IL-15. The binding of IL-10 to its receptor complex activates the JAK1 and Tyk2 kinases and involves STAT3 and STAT1.…”

Section: Caspase-independentmentioning

confidence: 99%

Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

et al. 2003

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Studies of human immunodeficiency virus (HIV) and nonhuman primate models of pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infections have suggested that enhanced ex vivo CD4 T-cell death is a feature of pathogenic infection in vivo. However, the relative contributions of the extrinsic and intrinsic pathways to programmed T-cell death in SIV infection have not been studied. We report here that the spontaneous death rate of CD4 þ T cells from pathogenic SIVmac251-infected rhesus macaques ex vivo is correlated with CD4 T-cell depletion and plasma viral load in vivo. CD4 þ T cells from SIVmac251-infected macaques showed upregulation of the death ligand (CD95L) and of the proapoptotic proteins Bim and Bak, but not of Bax. Both CD4 þ and CD8 þ T cells from SIVmac251-infected macaques underwent caspase-dependent death following CD95 ligation. The spontaneous death of CD4 þ and CD8 þ T cells was not prevented by a decoy CD95 receptor or by a broad-spectrum caspase inhibitor (zVADfmk), suggesting that this form of cell death is independent of CD95/CD95L interaction and caspase activation. IL-2 and IL-15 prevented the spontaneous death of CD4 þ and CD8 þ T cells, whereas IL-10 prevented only CD8 T-cell death and IL-7 had no effect on T-cell death. Our results indicate that caspasedependent and caspase-independent pathways are involved in the death of T cells in pathogenic SIVmac251-infected primates.

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Section: Caspase-independentmentioning

confidence: 99%

Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

et al. 2003

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“…Moreover, IL-10 stimulates the growth of B cells (6) and serves as a cofactor with IL-2, IL-4, and IL-7 in promoting the growth of murine thymocytes as well as mature T cells (7), and with IL-3 or IL-4 in stimulating proliferation of mast cells (8). IL-10 has been reported to prevent the apoptotic cell death of IL-2-dependent T cells and germinal center B cells (9,10).…”

Section: Nterleukin 10 Produced By T Cells B Cells or Monocytes/ mentioning

confidence: 99%

IL-10 Inhibits Granulocyte-Macrophage Colony-Stimulating Factor-Dependent Human Monocyte Survival at the Early Stage of the Culture and Inhibits the Generation of Macrophages

Hashimoto

Komuro²,

Yamada

et al. 2001

The Journal of Immunology

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We previously demonstrated that IL-10 alone does not stimulate growth and differentiation of human monocytes, but enhances those of monocytes stimulated with M-CSF. We studied here the effect of IL-10 on human monocytes stimulated with GM-CSF. Monocytes stimulated with GM-CSF alone survived and developed into macrophages. Monocytes cultured with GM-CSF plus IL-10, however, died through apoptosis. IL-10 decreased expression of bcl-2, bcl-xL, and mcl-1- but not bax mRNA in monocytes stimulated with GM-CSF. IL-10 did not change the expression of mRNA of both GM-CSFR α-chain and β-chain, but inhibited tyrosine phosphorylation of STAT5 and extracellular signal-regulated kinases 1 and 2 in the monocytes. The inhibitory effect of IL-10 was restricted to treatment 48 h after stimulation with GM-CSF. Addition of IL-10 after that time induced neither apoptosis nor a decrease in expression of bcl-2, bcl-xL, and mcl-1 mRNA. IL-10, however, inhibited LPS-induced TNF-α production even in these cells, indicating that the cells still possessed responsiveness to IL-10. Monocytes pretreated for >48 h with GM-CSF became resistant to GM-CSF withdrawal, and the cells could survive without GM-CSF. These results indicate that IL-10 selectively inhibits GM-CSF-dependent monocyte survival by inhibiting the signaling events induced by GM-CSF, but the timing of addition of IL-10 is critical, and IL-10 had to be added within 48 h after stimulation with GM-CSF to achieve the inhibitory effect. These results taken together with our previous results indicate that IL-10 plays a pivotal role in monocyte survival and development into macrophages in concert with M-CSF and GM-CSF.

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“…Induction of apoptosis can be initiated or prevented by signals though cell membrane proteins (CD2, CD3, CD4 or others) or by soluble factors like interleukin (IL)-2, IL-7, IL-4, G-or GM-CSF [14][15][16][17][18][19][20][21][22][23][24][25]. Programmed cell death seems to be of central importance, not only for the well balanced function of the immune system.…”

Section: Introductionmentioning

confidence: 99%

Differential Role for IL‐2 and IL‐15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes

et al. 1997

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Lorenz H-M, Hieronymus T, Grünke M, Manger B, Kalden JR. Differential Role for IL-2 and IL-15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes. Scand J Immunol 1997;45:660-669 Interleukin (IL)-15 is a newly described cytokine with properties similar to IL-2. Even though it does not share sequence homology with IL-2, both cytokines bind to the same receptor with the noted exception of a cytokine specific a-chain. In this study the authors compared IL-2 and IL-15 to determine their ability to rescue short term activated lymphocytes (phytohaemagglutinin stimulation of peripheral blood mononuclear cells for 6 days, followed by expansion in medium containing IL-2 for 2 days) from apoptotic cell death. The authors found that both IL-2 and IL-15 can inhibit induction of apoptosis in this experimental model with similar time and dose kinetics. On mRNA or protein levels induction of pro-and anti-apoptotic gene products like fasL, bcl-2, or bax with minor effects on fas/Apo-1 or bcl-x L was observed under culture conditions with both IL-2 and IL-15. Next, it was found that phytohaemagglutinin (PHA) blasts were less responsive (in terms of cellular proliferation and prevention from apoptosis) to IL-2 if signals through the a-chain were blocked, with no effect on b-chain specific monoclonal antibodies (MoAb). By contrast, IL-15 was less effective in induction of cellular proliferation and prevention of apoptosis if IL-2R b-chain specific MoAb were added to cell cultures. Testing intracellular signalling induced by IL-2 or IL-15, the authors found identical changes in tyrosine phosphorylation patterns in PHA blasts cultured in medium or under IL-2 or IL-15 stimulation. By contrast, they found consistent differences if PHA stimulated peripheral blood mononuclear cells (PBMC) were expanded in medium containing IL-15 (instead of IL-2). These IL-15 expanded PHA blasts showed a significantly increased percentage of apoptosis after growth factor withdrawal. Furthermore, IL-2 was more efficient than IL-15 in rescuing IL-15 expanded PHA blasts from apoptosis. In IL-15 expanded PHA blasts expression of IL-2R a-chain was lower than that in IL-2 expanded PHA blasts. A model presenting a differential role for IL-2 and IL-15 in inhibition of apoptosis in vivo is discussed.

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IL-10 inhibits apoptotic cell death in human T cells starved of IL-2

Cited by 115 publications

References 0 publications

Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

Caspase-dependent and -independent T-cell death pathways in pathogenic simian immunodeficiency virus infection: relationship to disease progression

IL-10 Inhibits Granulocyte-Macrophage Colony-Stimulating Factor-Dependent Human Monocyte Survival at the Early Stage of the Culture and Inhibits the Generation of Macrophages

Differential Role for IL‐2 and IL‐15 in the Inhibition of Apoptosis in Short Term Activated Human Lymphocytes

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