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IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-γ response that is regulated by CD8+ T cells

Sayeh, Ebrahim ; Sterling, Katherine ; Speck, Edwin ; Freedman, John and Semple, John W. LU (2004) In Blood 103(7). p.2705-2709
Abstract

The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic platelets are poorly understood. We studied the role that murine recipient CD8+ T and natural killer (NK) cells play in immunity against allogeneic platelets. BALB/c mice were depleted of the cells by cell-specific antibodies, transfused weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were measured by flow cytometry. While allogeneic platelet transfusions into wild-type recipients stimulated IgG antidonor antibodies in all mice by the fifth transfusion, CD8-depleted mice had significantly (P < .001) enhanced antibody production. Isotype analysis revealed that CD8+ T cells suppressed T-helper 2... (More)

The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic platelets are poorly understood. We studied the role that murine recipient CD8+ T and natural killer (NK) cells play in immunity against allogeneic platelets. BALB/c mice were depleted of the cells by cell-specific antibodies, transfused weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were measured by flow cytometry. While allogeneic platelet transfusions into wild-type recipients stimulated IgG antidonor antibodies in all mice by the fifth transfusion, CD8-depleted mice had significantly (P < .001) enhanced antibody production. Isotype analysis revealed that CD8+ T cells suppressed T-helper 2 (Th2)-associated IgG1 but enhanced Th1-associated IgG2a. Compared with wild-type mice, platelet transfusions into CD8-depleted mice stimulated enhanced intracellular interferon (IFN)-γ production by CD4- lymphocytes within 24 hours after the first transfusion. The early IFN-γ response correlated with nitric oxide-dependent splenic cytotoxicity (P < .001). In asialo ganglioside monosialic acid 1 (GM1)-depleted mice transfused with allogeneic platelets, the IFN-γ production, splenic cytotoxicity, and IgG antidonor antibody response were significantly suppressed. These results demonstrate that IgG antiplatelet immunity is dependent on an early NK cell-derived IFN-γ response that is negatively regulated by CD8+ T cells and suggest that targeting Innate NK cell responses may significantly reduce platelet alloimmunization.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Blood
volume
103
issue
7
pages
2705 - 2709
publisher
American Society of Hematology
external identifiers
  • pmid:14656873
  • scopus:1642384187
ISSN
0006-4971
DOI
10.1182/blood-2003-10-3552
language
English
LU publication?
no
id
a2e8a407-63ca-4a35-87e8-145c6db8eac2
date added to LUP
2019-12-03 10:21:53
date last changed
2024-07-24 10:21:43
@article{a2e8a407-63ca-4a35-87e8-145c6db8eac2,
  abstract     = {{<p>The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic platelets are poorly understood. We studied the role that murine recipient CD8<sup>+</sup> T and natural killer (NK) cells play in immunity against allogeneic platelets. BALB/c mice were depleted of the cells by cell-specific antibodies, transfused weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were measured by flow cytometry. While allogeneic platelet transfusions into wild-type recipients stimulated IgG antidonor antibodies in all mice by the fifth transfusion, CD8-depleted mice had significantly (P &lt; .001) enhanced antibody production. Isotype analysis revealed that CD8<sup>+</sup> T cells suppressed T-helper 2 (Th2)-associated IgG1 but enhanced Th1-associated IgG2a. Compared with wild-type mice, platelet transfusions into CD8-depleted mice stimulated enhanced intracellular interferon (IFN)-γ production by CD4<sup>-</sup> lymphocytes within 24 hours after the first transfusion. The early IFN-γ response correlated with nitric oxide-dependent splenic cytotoxicity (P &lt; .001). In asialo ganglioside monosialic acid 1 (GM1)-depleted mice transfused with allogeneic platelets, the IFN-γ production, splenic cytotoxicity, and IgG antidonor antibody response were significantly suppressed. These results demonstrate that IgG antiplatelet immunity is dependent on an early NK cell-derived IFN-γ response that is negatively regulated by CD8<sup>+</sup> T cells and suggest that targeting Innate NK cell responses may significantly reduce platelet alloimmunization.</p>}},
  author       = {{Sayeh, Ebrahim and Sterling, Katherine and Speck, Edwin and Freedman, John and Semple, John W.}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{7}},
  pages        = {{2705--2709}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-γ response that is regulated by CD8<sup>+</sup> T cells}},
  url          = {{http://dx.doi.org/10.1182/blood-2003-10-3552}},
  doi          = {{10.1182/blood-2003-10-3552}},
  volume       = {{103}},
  year         = {{2004}},
}