Unique processing pathways within recipient antigen-presenting cells determine IgG immunity against donor platelet MHC antigens
(2000) In Blood 95(5). p.1735-1742- Abstract
Recipient IgG immunity against leukoreduced donor platelets is dependent on indirect T-cell allorecognition and is suppressed in vivo by inhibitors (aminoguanidine, AMG) of inducible nitric oxide synthase (INOS). To examine recipient processing pathways of donor platelet antigens, enriched macrophages (antigenpresenting cells [APC]) from BALB/c (H-2(d)) mice were pulsed with allogeneic C57BL/6 (H-2(b)) platelets and transfused weekly into naive BALB/c mice. Platelet-pulsed APC stimulated IgG antidonor antibody production in 45% of recipients by the second transfusion and in 100% by the sixth transfusion; this response was enhanced by pulsing in the presence of interferon-γ. By the sixth transfusion, high-titer IgG1 (mean titer 4990) and... (More)
Recipient IgG immunity against leukoreduced donor platelets is dependent on indirect T-cell allorecognition and is suppressed in vivo by inhibitors (aminoguanidine, AMG) of inducible nitric oxide synthase (INOS). To examine recipient processing pathways of donor platelet antigens, enriched macrophages (antigenpresenting cells [APC]) from BALB/c (H-2(d)) mice were pulsed with allogeneic C57BL/6 (H-2(b)) platelets and transfused weekly into naive BALB/c mice. Platelet-pulsed APC stimulated IgG antidonor antibody production in 45% of recipients by the second transfusion and in 100% by the sixth transfusion; this response was enhanced by pulsing in the presence of interferon-γ. By the sixth transfusion, high-titer IgG1 (mean titer 4990) and IgG2a (1933) isotypes specific for donor major histocompatibility complex (MHC) class I antigens were detected. Platelet pulsing in the presence of AMG or colchicine significantly inhibited the ability of APC to stimulate IgG alloantibodies; only 50% (P < .005) and 20% (P < .0001) of recipients, respectively, produced antibodies by the sixth transfusion. AMG inhibition was reversed by the addition of L-arginine, the substrate for INOS. In contrast, pulsing in the presence of chloroquine, the proteasome inhibitory peptide MG115, or Brefeldin A enhanced APC immunity (70-100% of recipients antibody positive by the second transfusion [P < .05]); these agents allowed the pulsed APC to stimulate IgG2a but inhibited IgG1 production and this correlated with a reduction In serum interleukin (IL)-4 levels. The results suggest that for donor platelet antigens to stimulate IgG alloantibodies, recipient APC use the essential generation of nitric oxide and a noncytosolic, pH-independent processing pathway, which can be exploited as an effective immunotherapy target to further inhibit alloimmunization against leukoreduced platelets. (C) 2000 by The American Society of Hematology.
(Less)
- author
- Bang, K. W.Annie ; Speck, Edwin R. ; Blanchette, Victor S. ; Freedman, John and Semple, John W. LU
- publishing date
- 2000-03-01
- type
- Contribution to journal
- publication status
- published
- in
- Blood
- volume
- 95
- issue
- 5
- pages
- 8 pages
- publisher
- American Society of Hematology
- external identifiers
-
- scopus:0034161583
- pmid:10688832
- ISSN
- 0006-4971
- language
- English
- LU publication?
- no
- id
- 804e9654-2c3c-4c56-8979-4c1175afedeb
- date added to LUP
- 2019-12-03 10:27:58
- date last changed
- 2024-03-04 09:28:18
@article{804e9654-2c3c-4c56-8979-4c1175afedeb,
abstract = {{<p>Recipient IgG immunity against leukoreduced donor platelets is dependent on indirect T-cell allorecognition and is suppressed in vivo by inhibitors (aminoguanidine, AMG) of inducible nitric oxide synthase (INOS). To examine recipient processing pathways of donor platelet antigens, enriched macrophages (antigenpresenting cells [APC]) from BALB/c (H-2(d)) mice were pulsed with allogeneic C57BL/6 (H-2(b)) platelets and transfused weekly into naive BALB/c mice. Platelet-pulsed APC stimulated IgG antidonor antibody production in 45% of recipients by the second transfusion and in 100% by the sixth transfusion; this response was enhanced by pulsing in the presence of interferon-γ. By the sixth transfusion, high-titer IgG1 (mean titer 4990) and IgG2a (1933) isotypes specific for donor major histocompatibility complex (MHC) class I antigens were detected. Platelet pulsing in the presence of AMG or colchicine significantly inhibited the ability of APC to stimulate IgG alloantibodies; only 50% (P < .005) and 20% (P < .0001) of recipients, respectively, produced antibodies by the sixth transfusion. AMG inhibition was reversed by the addition of L-arginine, the substrate for INOS. In contrast, pulsing in the presence of chloroquine, the proteasome inhibitory peptide MG115, or Brefeldin A enhanced APC immunity (70-100% of recipients antibody positive by the second transfusion [P < .05]); these agents allowed the pulsed APC to stimulate IgG2a but inhibited IgG1 production and this correlated with a reduction In serum interleukin (IL)-4 levels. The results suggest that for donor platelet antigens to stimulate IgG alloantibodies, recipient APC use the essential generation of nitric oxide and a noncytosolic, pH-independent processing pathway, which can be exploited as an effective immunotherapy target to further inhibit alloimmunization against leukoreduced platelets. (C) 2000 by The American Society of Hematology.</p>}},
author = {{Bang, K. W.Annie and Speck, Edwin R. and Blanchette, Victor S. and Freedman, John and Semple, John W.}},
issn = {{0006-4971}},
language = {{eng}},
month = {{03}},
number = {{5}},
pages = {{1735--1742}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Unique processing pathways within recipient antigen-presenting cells determine IgG immunity against donor platelet MHC antigens}},
volume = {{95}},
year = {{2000}},
}