PMID- 10894360
OWN - NLM
STAT- MEDLINE
DCOM- 20001120
LR  - 20111117
IS  - 1525-8165 (Print)
IS  - 1525-8165 (Linking)
VI  - 9
IP  - 3
DP  - 2000 Jun
TI  - Upregulation of interleukin-10 and inhibition of alloantigen responses by 
      transferrin and transferrin-derived glycans.
PG  - 381-92
AB  - Previous studies have shown that critically timed administration of transferrin 
      (Tf) facilitates induction of immunologic unresponsiveness. Here, we determined 
      in mixed leukocyte culture (MLC) and in concanavalin A (ConA)-driven cultures the 
      effect of exogenous Tf and Tf-derived glycans (Tf-Gly) on lymphocyte 
      proliferation. In cultures of human blood lymphocytes, Tf inhibited selectively 
      alloantigen-driven proliferation in MLC, but not ConA-stimulated lymphocyte 
      proliferation. Deglycosylation of Tf abrogated the inhibitory effect of Tf on 
      alloantigen-induced lymphocyte proliferation, and, consistent with a role for 
      glycans, an effect qualitatively and quantitatively similar to Tf was exerted by 
      purified Tf-Gly. Glycans isolated from other proteins, for example, 
      immunoglobulin G (IgG) or fibrinogen, failed to inhibit alloantigen-induced 
      proliferation selectively. Rather, they suppressed lymphocyte proliferation in a 
      non-specific manner. Determination of cytokines in MLC supernatant showed a 
      downregulation of interleukin-1beta (IL-1beta), 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 observed effects of Tf and Tf-Gly on 
      alloantigen-induced lymphocyte proliferation. The effect of Tf on MLC was 
      directly IL-10-dependent. IL-10 levels were inversely correlated with lymphocyte 
      proliferation and CD86 expression. Neutralization of IL-10 by anti-IL-10 
      monoclonal antibody (mAb) blocked the effect of Tf. The MLC-modulating effect of 
      Tf (or Tf-Gly) was not dependent upon the Tf receptor CD71 but appeared to be 
      mediated by a Gly-responsive receptor. These data suggest a role of Tf, and, in 
      particular, Tf-Gly, in allo-interactions that is independent from the role of Tf 
      in iron metabolism, and appears to involve co-stimulatory signals.
FAU - Lesnikova, M
AU  - Lesnikova M
AD  - Fred Hutchinson Cancer Research Center and University of Washington, Seattle 
      98109-1024, USA.
FAU - Lesnikov, V
AU  - Lesnikov V
FAU - Arrighi, S
AU  - Arrighi S
FAU - Kistler, G
AU  - Kistler G
FAU - Pierpaoli, W
AU  - Pierpaoli W
FAU - Deeg, H J
AU  - Deeg HJ
LA  - eng
GR  - HL36444/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Hematother Stem Cell Res
JT  - Journal of hematotherapy & stem cell research
JID - 100892915
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, B-Lymphocyte)
RN  - 0 (CD71 antigen)
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Isoantigens)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, Transferrin)
RN  - 0 (Transferrin)
RN  - 11028-71-0 (Concanavalin A)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antigens, CD/immunology/pharmacology
MH  - Antigens, Differentiation, B-Lymphocyte/immunology/pharmacology
MH  - Concanavalin A/pharmacology
MH  - Cytokines/biosynthesis/drug effects
MH  - Humans
MH  - Immunoglobulin G/pharmacology
MH  - Interleukin-10/genetics/immunology/*physiology
MH  - Isoantigens/*drug effects/immunology
MH  - Lymphocyte Activation/drug effects
MH  - Lymphocyte Culture Test, Mixed
MH  - Polysaccharides/*pharmacology
MH  - Receptors, Transferrin
MH  - Transferrin/analogs & derivatives/*pharmacology
MH  - Up-Regulation/*drug effects
EDAT- 2000/07/14 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/07/14 11:00
PHST- 2000/07/14 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/07/14 11:00 [entrez]
AID - 10.1089/15258160050079498 [doi]
PST - ppublish
SO  - J Hematother Stem Cell Res. 2000 Jun;9(3):381-92. doi: 10.1089/15258160050079498.