Upregulation of interleukin-10 and inhibition of alloantigen responses by transferrin and transferrin-derived glycans

Citation
M. Lesnikova et al., Upregulation of interleukin-10 and inhibition of alloantigen responses by transferrin and transferrin-derived glycans, J HEMATH ST, 9(3), 2000, pp. 381-392
Citations number
62
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH
ISSN journal
15258165 → ACNP
Volume
9
Issue
3
Year of publication
2000
Pages
381 - 392
Database
ISI
SICI code
1525-8165(200006)9:3<381:UOIAIO>2.0.ZU;2-K
Abstract
Previous studies have shown that critically timed administration of transfe rrin (Tf) facilitates induction of immunologic unresponsiveness. Here, we d etermined in mixed leukocyte culture (MLC) and in concanavalin A (ConA)-dri ven cultures the effect of exogenous Tf and Tf-derived glycans (Tf-Gly) on lymphocyte proliferation. In cultures of human blood lymphocytes, Tf inhibi ted selectively alloantigen-driven proliferation in MLC, but not ConA-stimu lated lymphocyte proliferation. Deglycosylation of Tf abrogated the inhibit ory effect of Tf on alloantigen-induced lymphocyte proliferation, and, cons istent with a role for glycans, an effect qualitatively and quantitatively similar to Tf was exerted by purified Tf-Gly. Glycans isolated from other p roteins, for example, immunoglobulin G (IgG) or fibrinogen, failed to inhib it alloantigen-induced proliferation selectively. Rather, they suppressed l ymphocyte proliferation in a non-specific manner. Determination of cytokine s in MLC supernatant showed a downregulation of interleukin-1 beta (IL-1 be ta), tumor necrosis factor-alpha (TNF-alpha), IL-2, and IL-12 (p40), along with an upregulation of IL-10, a pattern entirely consistent with the obser ved effects of Tf and Tf-Gly on alloantigen-induced lymphocyte proliferatio n. The effect of Tf on MLC was directly IL-10-dependent. IL-10 levels were inversely correlated with lymphocyte proliferation and CD86 expression. Neu tralization of IL-10 by anti-IL-10 monoclonal antibody (mAb) blocked the ef fect of Tf. The MLC-modulating effect of Tf (or Tf-Gly) was not dependent u pon the Tf receptor CD71 but appeared to be mediated by a Gly-responsive re ceptor. These data suggest a role of Tf, and, in particular, Tf-Gly, in all o-interactions that is independent from the role of Tf in iron metabolism, and appears to involve co-stimulatory signals.