PMID- 18256920
OWN - NLM
STAT- MEDLINE
DCOM- 20080530
LR  - 20211203
IS  - 1058-0468 (Print)
IS  - 1573-7330 (Electronic)
IS  - 1058-0468 (Linking)
VI  - 25
IP  - 2-3
DP  - 2008 Feb-Mar
TI  - CD200-dependent and nonCD200-dependent pathways of NK cell suppression by human 
      IVIG.
PG  - 67-72
LID - 10.1007/s10815-008-9202-9 [doi]
AB  - PROBLEM: Intravenous immunoglobulin (IVIG) has been used to suppress autoimmune 
      and inflammatory disorders by a variety of mechanisms. Recently, the CD200 
      tolerance-promoting signal has been found to play a role in IVIG suppression of 
      blood natural killer (NK) cells. Further, different types of IVIG have been 
      reported to differ in this activity, and that has been related to efficacy (and 
      inefficacy) of treatment of women with pregnancy failure. CD200 acts by binding 
      to CD200 receptors (C200R). The objective of this study was to determine if 
      CD200-dependent NK suppression by IVIG involved direct binding of IVIG-associated 
      CD200 molecules to CD200R on NK cells. METHOD OF STUDY: Peripheral Blood 
      Lymphocytes isolated from human blood were used as a source of NK cells to lyse 
      Cr(51)-labelled K562 target cells in vitro in 18 and 4 h assays, and three 
      different types of IVIG were tested for suppressive activity in the presence or 
      absence of specific monoclonal anti-huCD200. In some experiments, CD56(+) NK 
      cells were purified using anti-CD56 magnetic beads. Western blotting of IVIG 
      using a specific anti-huCD200 antibody was done. Enzyme-Linked ImmunoSorbent 
      Assays were used to measure cytokine production in NK assays. RESULTS: Different 
      IVIGs showed significant differences in potency in suppressing NK cytolytic 
      activity in vitro (mg/ml for 60% suppression, Gammagard 4.1, Gamunex 14.1, 
      Gamimmune 20.2). For CD200-dependent suppression, Gammagard was twice as potent 
      as Gamimmune, but equivalent to Gamunex. The presence of suppression in 4 hour 
      assays indicated stimulation of cytokine synthesis was unlikely to explain 
      CD200-dependent suppression. Purification of NK cells led to loss of the 
      CD200-dependent component. Western blotting confirmed that material reactive with 
      anti-CD200 antibody was present in Immunoglobulin G (IgG) preparations, and at a 
      lower level in human serum that contains IgG. CONCLUSIONS: IVIGs are not all 
      equipotent in suppressing NK cell cytolytic activity. CD200 associated with IVIG 
      is an important component of suppression. CD200-dependent suppression appears to 
      be mediated by a non-NK population that then acts on NK cells by direct contact 
      rather than indirectly through release of immunosuppressive cytokines.
FAU - Clark, David A
AU  - Clark DA
AD  - Department of Medicine, McMaster University, 1200 Main St. West., Hamilton, ON 
      L8N 3Z5, Canada. clarkd@mcmaster.ca
FAU - Wong, Karrie
AU  - Wong K
FAU - Banwatt, Daljeet
AU  - Banwatt D
FAU - Chen, Ziqhi
AU  - Chen Z
FAU - Liu, Jian
AU  - Liu J
FAU - Lee, Lydia
AU  - Lee L
FAU - Gorczynski, Reginald M
AU  - Gorczynski RM
FAU - Blajchman, Morris A
AU  - Blajchman MA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080207
PL  - Netherlands
TA  - J Assist Reprod Genet
JT  - Journal of assisted reproduction and genetics
JID - 9206495
RN  - 0 (Antigens, CD)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - UQ4V77A8VA (antigens, CD200)
SB  - IM
MH  - Antigens, CD/*physiology
MH  - Cell Line
MH  - Cell Separation
MH  - Female
MH  - Humans
MH  - Immunoglobulins, Intravenous/classification/*therapeutic use
MH  - *Immunosuppression Therapy
MH  - Killer Cells, Natural/cytology/*immunology
MH  - Pregnancy
MH  - Signal Transduction/*immunology
PMC - PMC2582113
EDAT- 2008/02/08 09:00
MHDA- 2008/05/31 09:00
PMCR- 2009/03/01
CRDT- 2008/02/08 09:00
PHST- 2007/12/03 00:00 [received]
PHST- 2008/01/14 00:00 [accepted]
PHST- 2008/02/08 09:00 [pubmed]
PHST- 2008/05/31 09:00 [medline]
PHST- 2008/02/08 09:00 [entrez]
PHST- 2009/03/01 00:00 [pmc-release]
AID - 9202 [pii]
AID - 10.1007/s10815-008-9202-9 [doi]
PST - ppublish
SO  - J Assist Reprod Genet. 2008 Feb-Mar;25(2-3):67-72. doi: 
      10.1007/s10815-008-9202-9. Epub 2008 Feb 7.