Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires

Neil Thomas Young, D L Roelen, N Iggo, D W Gray, J A Roake, V Graham, K J Wood, M J Dallman, K I Welsh, P J Morris

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Pretransplant blood transfusion has a well-known beneficial effect on posttransplant graft survival. Recently, it has been proposed that the clinical benefit of transfusion is due to HLA-DR antigen sharing between the blood donor(s) and the recipient. Immunological studies have suggested that this might result from a functional deletion of donor-reactive cytotoxic T lymphocytes. METHODS: We investigated frequencies of alloreactive lymphocyte precursors with cytotoxic or interleukin-2-producing helper function by limiting dilution analysis in 10 renal dialysis patients before and after transfusion with fresh, allogeneic whole blood. Five patients received blood transfusions from donors matched for one HLA haplotype (or one HLA-B-DR antigen) and the other five patients received blood from fully HLA-mismatched donors. RESULTS: Contrary to some previous reports, frequency analysis of cytotoxic T lymphocyte precursors revealed no significant differences between the two treatment groups in terms of development of blood donor-specific hyporesponsiveness after transfusion. Split-well analysis of cytotoxic T lymphocyte precursors reactive with single-mismatched HLA antigens demonstrated that the effects of transfusion on alloreactive specificity are complex and may vary depending on the particular antigens mismatched between the recipient and blood donor. Analysis of donor-specific helper T lymphocyte precursor frequencies revealed a significant decrease of interleukin-2-producing cells 3 months after transfusion in the total patient population. This effect was most prominent in the recipients of HLA-mismatched blood, but it also exhibited some degree of nonspecificity, as frequencies of third-party reactive helper T lymphocyte precursors were also significantly reduced. CONCLUSIONS: Our overall results suggest that the degree of HLA matching between blood donor and recipient does not greatly influence the effect of blood transfusion on the T lymphocyte allorepertoire. The apparent induced down-regulation of helper T lymphocyte activity may play a role in the reported immunosuppressive effects of allogeneic blood transfusion.
Original languageEnglish
Pages (from-to)1160-1165
Number of pages6
JournalTransplantation
Volume63
Issue number8
Publication statusPublished - 27 Apr 1997

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Blood Donors
Blood Transfusion
Haplotypes
T-Lymphocytes
Cytotoxic T-Lymphocytes
Helper-Inducer T-Lymphocytes
Tissue Donors
HLA-DR Antigens
Interleukin-2
HLA-B Antigens
Graft Survival
Immunosuppressive Agents
HLA Antigens
Renal Dialysis
Down-Regulation
Lymphocytes
Antigens
Population
Therapeutics

Keywords

  • Adult
  • Blood Donors
  • Blood Grouping and Crossmatching
  • Blood Transfusion
  • Cell Count
  • HLA Antigens
  • Haplotypes
  • Humans
  • Isoantigens
  • Male
  • Middle Aged
  • Stem Cells
  • T-Lymphocytes
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes, Helper-Inducer
  • Time Factors

Cite this

Young, N. T., Roelen, D. L., Iggo, N., Gray, D. W., Roake, J. A., Graham, V., ... Morris, P. J. (1997). Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires. Transplantation, 63(8), 1160-1165.

Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires. / Young, Neil Thomas; Roelen, D L; Iggo, N; Gray, D W; Roake, J A; Graham, V; Wood, K J; Dallman, M J; Welsh, K I; Morris, P J.

In: Transplantation, Vol. 63, No. 8, 27.04.1997, p. 1160-1165.

Research output: Contribution to journalArticle

Young, NT, Roelen, DL, Iggo, N, Gray, DW, Roake, JA, Graham, V, Wood, KJ, Dallman, MJ, Welsh, KI & Morris, PJ 1997, 'Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires', Transplantation, vol. 63, no. 8, pp. 1160-1165.
Young NT, Roelen DL, Iggo N, Gray DW, Roake JA, Graham V et al. Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires. Transplantation. 1997 Apr 27;63(8):1160-1165.
Young, Neil Thomas ; Roelen, D L ; Iggo, N ; Gray, D W ; Roake, J A ; Graham, V ; Wood, K J ; Dallman, M J ; Welsh, K I ; Morris, P J. / Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires. In: Transplantation. 1997 ; Vol. 63, No. 8. pp. 1160-1165.
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abstract = "BACKGROUND: Pretransplant blood transfusion has a well-known beneficial effect on posttransplant graft survival. Recently, it has been proposed that the clinical benefit of transfusion is due to HLA-DR antigen sharing between the blood donor(s) and the recipient. Immunological studies have suggested that this might result from a functional deletion of donor-reactive cytotoxic T lymphocytes. METHODS: We investigated frequencies of alloreactive lymphocyte precursors with cytotoxic or interleukin-2-producing helper function by limiting dilution analysis in 10 renal dialysis patients before and after transfusion with fresh, allogeneic whole blood. Five patients received blood transfusions from donors matched for one HLA haplotype (or one HLA-B-DR antigen) and the other five patients received blood from fully HLA-mismatched donors. RESULTS: Contrary to some previous reports, frequency analysis of cytotoxic T lymphocyte precursors revealed no significant differences between the two treatment groups in terms of development of blood donor-specific hyporesponsiveness after transfusion. Split-well analysis of cytotoxic T lymphocyte precursors reactive with single-mismatched HLA antigens demonstrated that the effects of transfusion on alloreactive specificity are complex and may vary depending on the particular antigens mismatched between the recipient and blood donor. Analysis of donor-specific helper T lymphocyte precursor frequencies revealed a significant decrease of interleukin-2-producing cells 3 months after transfusion in the total patient population. This effect was most prominent in the recipients of HLA-mismatched blood, but it also exhibited some degree of nonspecificity, as frequencies of third-party reactive helper T lymphocyte precursors were also significantly reduced. CONCLUSIONS: Our overall results suggest that the degree of HLA matching between blood donor and recipient does not greatly influence the effect of blood transfusion on the T lymphocyte allorepertoire. The apparent induced down-regulation of helper T lymphocyte activity may play a role in the reported immunosuppressive effects of allogeneic blood transfusion.",
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T1 - Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires

AU - Young, Neil Thomas

AU - Roelen, D L

AU - Iggo, N

AU - Gray, D W

AU - Roake, J A

AU - Graham, V

AU - Wood, K J

AU - Dallman, M J

AU - Welsh, K I

AU - Morris, P J

PY - 1997/4/27

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N2 - BACKGROUND: Pretransplant blood transfusion has a well-known beneficial effect on posttransplant graft survival. Recently, it has been proposed that the clinical benefit of transfusion is due to HLA-DR antigen sharing between the blood donor(s) and the recipient. Immunological studies have suggested that this might result from a functional deletion of donor-reactive cytotoxic T lymphocytes. METHODS: We investigated frequencies of alloreactive lymphocyte precursors with cytotoxic or interleukin-2-producing helper function by limiting dilution analysis in 10 renal dialysis patients before and after transfusion with fresh, allogeneic whole blood. Five patients received blood transfusions from donors matched for one HLA haplotype (or one HLA-B-DR antigen) and the other five patients received blood from fully HLA-mismatched donors. RESULTS: Contrary to some previous reports, frequency analysis of cytotoxic T lymphocyte precursors revealed no significant differences between the two treatment groups in terms of development of blood donor-specific hyporesponsiveness after transfusion. Split-well analysis of cytotoxic T lymphocyte precursors reactive with single-mismatched HLA antigens demonstrated that the effects of transfusion on alloreactive specificity are complex and may vary depending on the particular antigens mismatched between the recipient and blood donor. Analysis of donor-specific helper T lymphocyte precursor frequencies revealed a significant decrease of interleukin-2-producing cells 3 months after transfusion in the total patient population. This effect was most prominent in the recipients of HLA-mismatched blood, but it also exhibited some degree of nonspecificity, as frequencies of third-party reactive helper T lymphocyte precursors were also significantly reduced. CONCLUSIONS: Our overall results suggest that the degree of HLA matching between blood donor and recipient does not greatly influence the effect of blood transfusion on the T lymphocyte allorepertoire. The apparent induced down-regulation of helper T lymphocyte activity may play a role in the reported immunosuppressive effects of allogeneic blood transfusion.

AB - BACKGROUND: Pretransplant blood transfusion has a well-known beneficial effect on posttransplant graft survival. Recently, it has been proposed that the clinical benefit of transfusion is due to HLA-DR antigen sharing between the blood donor(s) and the recipient. Immunological studies have suggested that this might result from a functional deletion of donor-reactive cytotoxic T lymphocytes. METHODS: We investigated frequencies of alloreactive lymphocyte precursors with cytotoxic or interleukin-2-producing helper function by limiting dilution analysis in 10 renal dialysis patients before and after transfusion with fresh, allogeneic whole blood. Five patients received blood transfusions from donors matched for one HLA haplotype (or one HLA-B-DR antigen) and the other five patients received blood from fully HLA-mismatched donors. RESULTS: Contrary to some previous reports, frequency analysis of cytotoxic T lymphocyte precursors revealed no significant differences between the two treatment groups in terms of development of blood donor-specific hyporesponsiveness after transfusion. Split-well analysis of cytotoxic T lymphocyte precursors reactive with single-mismatched HLA antigens demonstrated that the effects of transfusion on alloreactive specificity are complex and may vary depending on the particular antigens mismatched between the recipient and blood donor. Analysis of donor-specific helper T lymphocyte precursor frequencies revealed a significant decrease of interleukin-2-producing cells 3 months after transfusion in the total patient population. This effect was most prominent in the recipients of HLA-mismatched blood, but it also exhibited some degree of nonspecificity, as frequencies of third-party reactive helper T lymphocyte precursors were also significantly reduced. CONCLUSIONS: Our overall results suggest that the degree of HLA matching between blood donor and recipient does not greatly influence the effect of blood transfusion on the T lymphocyte allorepertoire. The apparent induced down-regulation of helper T lymphocyte activity may play a role in the reported immunosuppressive effects of allogeneic blood transfusion.

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KW - Haplotypes

KW - Humans

KW - Isoantigens

KW - Male

KW - Middle Aged

KW - Stem Cells

KW - T-Lymphocytes

KW - T-Lymphocytes, Cytotoxic

KW - T-Lymphocytes, Helper-Inducer

KW - Time Factors

M3 - Article

C2 - 9133479

VL - 63

SP - 1160

EP - 1165

JO - Transplantation

JF - Transplantation

SN - 0041-1337

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ER -