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Transfusion-related immunomodulation by platelets is dependent on their expression of MHC Class I molecules and is independent of white cells

Aslam, Rukhsana; Speck, Edwin R; Kim, Michael; Freedman, John and Semple, John W LU (2008) In Transfusion 48(9). p.86-1778
Abstract

BACKGROUND: Transfusion-related immunomodulation (TRIM) has been correlated with the presence of white cells (WBCs) in blood transfusions, but the role of components such as platelets (PLTs) in mediating TRIM has not been extensively examined. We designed a murine PLT transfusion model to study whether leukoreduced PLTs mediate TRIM effects.

STUDY DESIGN AND METHODS: CBA recipient mice were administered four weekly transfusions of either fresh (4 hr) or aged (24 and 72 hr) donor leukoreduced PLTs from allogeneic BALB/c mice and then transplanted with skin grafts from donor-matched mice. TRIM was measured by comparing the times to graft rejection and these were correlated with immunoglobulin G (IgG) antibody development measured by... (More)

BACKGROUND: Transfusion-related immunomodulation (TRIM) has been correlated with the presence of white cells (WBCs) in blood transfusions, but the role of components such as platelets (PLTs) in mediating TRIM has not been extensively examined. We designed a murine PLT transfusion model to study whether leukoreduced PLTs mediate TRIM effects.

STUDY DESIGN AND METHODS: CBA recipient mice were administered four weekly transfusions of either fresh (4 hr) or aged (24 and 72 hr) donor leukoreduced PLTs from allogeneic BALB/c mice and then transplanted with skin grafts from donor-matched mice. TRIM was measured by comparing the times to graft rejection and these were correlated with immunoglobulin G (IgG) antibody development measured by flow cytometry.

RESULTS: Compared with nontransfused control recipients, four transfusions of fresh, extremely leukoreduced (<0.05 WBCs/mL), allogeneic PLTs significantly (p < 0.002) reduced the recipient's ability to reject donor-matched skin grafts (survival >49 days compared with <14 days in nontransfused controls) despite the presence of high-titered serum IgG donor antibodies. In contrast, however, aged PLTs or fresh PLTs devoid of MHC Class I molecules were unable to affect skin graft survival nor stimulate antibody production. The PLT age-related inability to induce TRIM was shown to be due to loss of PLT-associated MHC Class I molecules; soluble supernatant MHC molecules that were transfused were unable to induce TRIM.

CONCLUSION: These results suggest that fresh PLTs can induce TRIM independently of WBCs due to their MHC antigen expression whereas aging results in loss of MHC and ability to mediate TRIM. The findings support the concept that either active MHC removal from fresh PLTs or passive removal by, for example, storage, may reduce any deleterious effects of TRIM in transfusion recipients.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Blood Platelets, Histocompatibility Antigens Class I, Leukocytes, Mice, Models, Animal, Platelet Transfusion, Journal Article, Research Support, Non-U.S. Gov't
in
Transfusion
volume
48
issue
9
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • Scopus:50849142515
ISSN
1537-2995
DOI
10.1111/j.1537-2995.2008.01791.x
language
English
LU publication?
no
id
4bc44c92-06a6-462e-9d88-79eee608636d
date added to LUP
2016-09-23 12:09:57
date last changed
2016-10-13 05:14:18
@misc{4bc44c92-06a6-462e-9d88-79eee608636d,
  abstract     = {<p>BACKGROUND: Transfusion-related immunomodulation (TRIM) has been correlated with the presence of white cells (WBCs) in blood transfusions, but the role of components such as platelets (PLTs) in mediating TRIM has not been extensively examined. We designed a murine PLT transfusion model to study whether leukoreduced PLTs mediate TRIM effects.</p><p>STUDY DESIGN AND METHODS: CBA recipient mice were administered four weekly transfusions of either fresh (4 hr) or aged (24 and 72 hr) donor leukoreduced PLTs from allogeneic BALB/c mice and then transplanted with skin grafts from donor-matched mice. TRIM was measured by comparing the times to graft rejection and these were correlated with immunoglobulin G (IgG) antibody development measured by flow cytometry.</p><p>RESULTS: Compared with nontransfused control recipients, four transfusions of fresh, extremely leukoreduced (&lt;0.05 WBCs/mL), allogeneic PLTs significantly (p &lt; 0.002) reduced the recipient's ability to reject donor-matched skin grafts (survival &gt;49 days compared with &lt;14 days in nontransfused controls) despite the presence of high-titered serum IgG donor antibodies. In contrast, however, aged PLTs or fresh PLTs devoid of MHC Class I molecules were unable to affect skin graft survival nor stimulate antibody production. The PLT age-related inability to induce TRIM was shown to be due to loss of PLT-associated MHC Class I molecules; soluble supernatant MHC molecules that were transfused were unable to induce TRIM.</p><p>CONCLUSION: These results suggest that fresh PLTs can induce TRIM independently of WBCs due to their MHC antigen expression whereas aging results in loss of MHC and ability to mediate TRIM. The findings support the concept that either active MHC removal from fresh PLTs or passive removal by, for example, storage, may reduce any deleterious effects of TRIM in transfusion recipients.</p>},
  author       = {Aslam, Rukhsana and Speck, Edwin R and Kim, Michael and Freedman, John and Semple, John W},
  issn         = {1537-2995},
  keyword      = {Animals,Blood Platelets,Histocompatibility Antigens Class I,Leukocytes,Mice,Models, Animal,Platelet Transfusion,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {9},
  pages        = {86--1778},
  publisher    = {ARRAY(0xa0534e0)},
  series       = {Transfusion},
  title        = {Transfusion-related immunomodulation by platelets is dependent on their expression of MHC Class I molecules and is independent of white cells},
  url          = {http://dx.doi.org/10.1111/j.1537-2995.2008.01791.x},
  volume       = {48},
  year         = {2008},
}