Apoptotic cells selectively suppress the Th1 cytokine interferon gamma in stimulated human peripheral blood mononuclear cells and shift the Th1/Th2 balance towards Th2.

Girkontaite I, Urbonaviciute V, Maseda D, Neubert K, Herrmann M, Voll RE
Autoimmunity. 2007 40 (4): 327-30

PMID: 17516220 · DOI:10.1080/08916930701356846

Apoptotic cells are readily recognized and engulfed by phagocytes and usually do not induce inflammation or tissue damage. Furthermore, they can actively suppress a pro-inflammatory response in phagocytes: In the presence of apoptotic cells, activated monocytes/macrophages produce more of the anti-inflammatory and immunoregulatory cytokines IL-10 and TGF-beta, but less of the pro-inflammatory cytokines TNFalpha, IL-1beta and IL-12. This immunoregulatory effect is most likely mediated by several receptors on monocytes/macrophages including the thrombospondin receptor (CD36). In addition to the modulation of cytokine secretion, apoptotic cell material inhibited the expression of MHC class II molecules on the surface of monocytes/macrophages. Decreased MHC II expression appeared to be mediated predominantly by increased IL-10 secretion in a para-/autocrine manner. Here, we show that the functional modulation of antigen-presenting monocytes/macrophages by apoptotic cells also influences T cell activation and function. When human peripheral blood mononuclear cells were stimulated with recall antigens in the presence of apoptotic cells, interferon gamma (IFN gamma) secretion was markedly suppressed, whereas secretion of the Th2 cytokine IL-4 was not significantly altered. Hence, apoptotic cells shift the T cell cytokine secretion pattern towards a Th2-like response. This Th2 shift can largely be prevented by neutralizing IL-10, indicating an important role of this cytokine for modulating T cell cytokine secretion patterns.

MeSH Terms (14)

Apoptosis Autocrine Communication Cells, Cultured Cytokines Histocompatibility Antigens Class II Humans Inflammation Mediators Interferon-gamma Lymphocyte Activation Paracrine Communication Phagocytes Phagocytosis Th1 Cells Th2 Cells

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