IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-γ response that is regulated by CD8+ T cells
(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.
(Less)
- author
- Sayeh, Ebrahim ; Sterling, Katherine ; Speck, Edwin ; Freedman, John and Semple, John W. LU
- publishing date
- 2004-04-01
- 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 < .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 < .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}}, }