Biological properties of interleukin 10

M Howard, A O'Garra - Immunology today, 1992 - cell.com
M Howard, A O'Garra
Immunology today, 1992cell.com
Interleukin 10 (IL-10)(Refs 1-3) O'Garra summarize what is currently IL-10-mediated
suppression of cytois an acid-sensitive protein of known of the biological properties of kine
synthesis also occurs when 35-40 kDa that is produced under IL-IO and speculate on its
clinical either TH1 T-cell clones a6 or natural different conditions of immune acti- potential,
killer (NK) cells 17 are activated by vation by the TH0 and TH2 subsets IL-2 and accessory
cells in an of helper T cells 1, 3, as well as by antigen-nonspecific, MHC-unrestricmonocytes …
Interleukin 10 (IL-10)(Refs 1-3) O'Garra summarize what is currently IL-10-mediated suppression of cytois an acid-sensitive protein of known of the biological properties of kine synthesis also occurs when 35-40 kDa that is produced under IL-IO and speculate on its clinical either TH1 T-cell clones a6 or natural different conditions of immune acti- potential, killer (NK) cells 17 are activated by vation by the TH0 and TH2 subsets IL-2 and accessory cells in an of helper T cells 1, 3, as well as by antigen-nonspecific, MHC-unrestricmonocytes, macrophages and B ted manner. This inhibition is also cells 4-6. IL-10 was initially dis-cytokine production 1, 3 and antigen-via an indirect action of IL-10 on the covered I and isolated2, 3 on the basis specific proliferation TM of cultured macrophage/monocyte population, of its ability to suppress cytokine clones of TH1 cells when they are suggesting modulation of other synthesis by Ti-tl helper T cells, activated in an accessory cell-effector mechanisms critical for While genomic analysis clearly con-dependent manner. Furthermore, in macrophage/monocyte accessory firms the mammalian origin of this some in vitro systems, the addition cell function. cytokine 2, 7, IL-10 displays remark-of anti-IL-10 antibodies to primary While these additional macroable homology to a previously un-cultures of helper T cells enhances phage/monocyte accessory cell effeccharacterized open reading frame, the emergence of cells bearing a Trtl-tor mechanisms have not yet been termed BCRF1, in the Epstein-Barr cell phenotype is. Collectively, these elucidated, numerous other effects virus (EBV) genome2, 3, 8. The protein data suggest that IL-10 may play a of IL-10 on cultured macrophage/encoded by BCRF1 (now designated role in diminishing delayed-type hy-monocytes have been defined. In vlL-10) exhibits partial IL-10 ac-persensitivity reactions and other the absence of any notable effect tivity 8, suggesting that EBV may Tial cell-mediated responses. The on the expression of a variety have captured this mammalian gene inhibition of TH1 cell development of macrophage/monocyte adhesion to confer some survival advantage and function is due to an indirect molecules 4, IL-10 nevertheless onitself. Theavailabilityofrecombi-action of IL-10 on a subpopulation causes a profound change in the nant mouse 2 and human 3 IL-10, to-of accessory cells rather than a morphology and adhesion of pergetherwithneutralizingmonoclonal direct action on the TH1 cells itoneal macrophages s or cultured antibodies that recognize these themselves 1, 14, 16. monocytes (R. de Waal Malefyt, proteins specifically 4, 9, has allowed IL-10 suppresses the ability of unpublished). IL-10 also inhibits identification of an array of murine macrophages, but not B cells, the production by macrophage/immunosuppressive and immuno-to stimulate THl-cell clones to monocytes of numerous inflammastimulatory properties associated synthesize cytokines 16. Similarly, tory mediators, including IL-lo~, with this cytokine, human monocyte-or mouse macro-IL-6, IL-8, granulocyte-macrophage phage-dependent proliferation of colony-stimulating factor (GM-Immunosuppressive properties of TH1 cells is also inhibited by CSF), granulocyte colony-stimu-IL-10 in vitro IL-10, while TH1 cell proliferation lating factor (G-CSF) and TNF-The helper T-cell compartment of induced by transformed human od, s, TM. In addition, endogenous IL-10 the immune system contains nu-B-cell lines 14 or murine dendritic suppresses synthesis of IL-10 by merous subpopulations that are cells (S. Macatonia and A. O'Garra, macrophages/monocytes 4, suggestdistinguishable on the basis of unpublished …
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