Long-term interleukin-10 presence induces the development of a novel, monocyte-derived cell type.
Interleukin (IL)-10 is one of the most crucial immunoregulatory cytokines. Its short-term effects have been analysed extensively, but little is known about its long-term effects. This is of considerable importance, as high systemic IL-10 levels are present for long periods in patients with persistent viral infections, certain cancers and in critical care patients. Our study investigated the effects of the long-term presence of IL-10 on human peripheral blood monocytes. In vitro, IL-10 treatment of these cells for 7 days induced the development of a novel cell type characterized by unique phenotypical and functional characteristics. These cells showed high HLA-DR expression and low expression of CD86 and other co-stimulatory molecules on their surface. The mRNA levels of both HLA-DR and CD86 were high, but no intracellular accumulation of CD86 protein was observed. With respect to its function, these cells showed strongly diminished tumour necrosis factor-alpha production following lipopolysaccharide stimulation, strongly diminished allogenic CD4(+) T cell stimulatory capacity, and even induced a hyporesponsive state in CD4(+) T cells. The phenotype remained stable despite the removal of IL-10. In vivo, we found monocytic cells from patients exhibiting this phenotype after long-term IL-10 exposure. These results complement our knowledge further about the biological effects of IL-10 and may provide an explanation for the sustained immunodeficiency in cases of the persistent presence of systemic IL-10.
Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany.
C
C
Schoenbein
W-D
WD
Docke
K
K
Wolk
G
G
Belbe
C
C
Hoflich
M
M
Jung
G
G
Grutz
W
W
Sterry
H-D
HD
Volk
K
K
Asadullah
R
R
Sabat
D000938:Antigen-Presenting Cells / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000276:immunology* / Q000627:therapeutic use; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha
D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D007519:Isoantigens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10