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
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.