Concomitant allorecognition of mismatched donor HLA class I- and class II- derived peptides in pediatric lung transplant recipients with bronchiolitis obliterans syndrome

Kim Lu, Andrés Jaramillo, Eric N. Mendeloff, Charles B. Huddleston, Stuart C. Sweet, G. Alexander Patterson, T. Mohanakumar

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: The authors' previous studies with 2 different adult patient populations demonstrated a correlation between indirect allorecognition of mismatched donor HLA Class I- and Class II-derived peptides and the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of this study was to determine whether a parallel allorecognition of mismatched donor HLA Class I- and Class II-derived peptides occurs after lung transplantation and to determine its correlation with the development of BOS after lung transplantation in a group of pediatric patients. Methods: Peripheral blood mononuclear cells from 7 BOS-positive and 6 BOS-negative pediatric lung transplant recipients (age, 11.5 ± 4.4 years) were cultured in the presence of synthetic peptides corresponding to the α-chain hypervariable regions of a mismatched donor HLA Class I molecule and the β-chain hypervariable region of a mismatched donor HLA-DR molecule. The frequencies of HLA Class I and Class II alloreactive T cells were determined using limiting dilution analysis. Results: A significant increase (p = 0.025) in HLA Class I-alloreactive T cells was observed in BOS-positive patients (7.1 × 10-5 ± 4.3 × 10-5) compared with BOS-negative patients (2.1 × 10-5 ± 1.8 × 10-6). In addition, a significant increase (p = 0.033) in HLA Class II-alloreactive T cells also was observed in BOS-positive patients (9.6 × 10-5 ± 7.9 × 10-5) compared with BOS-negative patients (1.3 × 10-5 ± 2.1 × 10-6). Conclusions: This study indicates that a parallel CD4+ T-cell alloreactivity to both donor HLA Class I and Class II molecules may play a role in the pathogenesis of BOS both in adult and pediatric lung transplant recipients.

Original languageEnglish (US)
Pages (from-to)35-43
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Bronchiolitis Obliterans
Tissue Donors
Pediatrics
Lung
Peptides
Lung Transplantation
T-Lymphocytes
Transplant Recipients
HLA-DR Antigens
Blood Cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

Concomitant allorecognition of mismatched donor HLA class I- and class II- derived peptides in pediatric lung transplant recipients with bronchiolitis obliterans syndrome. / Lu, Kim; Jaramillo, Andrés; Mendeloff, Eric N.; Huddleston, Charles B.; Sweet, Stuart C.; Patterson, G. Alexander; Mohanakumar, T.

In: Journal of Heart and Lung Transplantation, Vol. 22, No. 1, 01.01.2003, p. 35-43.

Research output: Contribution to journalArticle

Lu, Kim ; Jaramillo, Andrés ; Mendeloff, Eric N. ; Huddleston, Charles B. ; Sweet, Stuart C. ; Patterson, G. Alexander ; Mohanakumar, T. / Concomitant allorecognition of mismatched donor HLA class I- and class II- derived peptides in pediatric lung transplant recipients with bronchiolitis obliterans syndrome. In: Journal of Heart and Lung Transplantation. 2003 ; Vol. 22, No. 1. pp. 35-43.
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abstract = "Background: The authors' previous studies with 2 different adult patient populations demonstrated a correlation between indirect allorecognition of mismatched donor HLA Class I- and Class II-derived peptides and the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of this study was to determine whether a parallel allorecognition of mismatched donor HLA Class I- and Class II-derived peptides occurs after lung transplantation and to determine its correlation with the development of BOS after lung transplantation in a group of pediatric patients. Methods: Peripheral blood mononuclear cells from 7 BOS-positive and 6 BOS-negative pediatric lung transplant recipients (age, 11.5 ± 4.4 years) were cultured in the presence of synthetic peptides corresponding to the α-chain hypervariable regions of a mismatched donor HLA Class I molecule and the β-chain hypervariable region of a mismatched donor HLA-DR molecule. The frequencies of HLA Class I and Class II alloreactive T cells were determined using limiting dilution analysis. Results: A significant increase (p = 0.025) in HLA Class I-alloreactive T cells was observed in BOS-positive patients (7.1 × 10-5 ± 4.3 × 10-5) compared with BOS-negative patients (2.1 × 10-5 ± 1.8 × 10-6). In addition, a significant increase (p = 0.033) in HLA Class II-alloreactive T cells also was observed in BOS-positive patients (9.6 × 10-5 ± 7.9 × 10-5) compared with BOS-negative patients (1.3 × 10-5 ± 2.1 × 10-6). Conclusions: This study indicates that a parallel CD4+ T-cell alloreactivity to both donor HLA Class I and Class II molecules may play a role in the pathogenesis of BOS both in adult and pediatric lung transplant recipients.",
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AU - Lu, Kim

AU - Jaramillo, Andrés

AU - Mendeloff, Eric N.

AU - Huddleston, Charles B.

AU - Sweet, Stuart C.

AU - Patterson, G. Alexander

AU - Mohanakumar, T.

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AB - Background: The authors' previous studies with 2 different adult patient populations demonstrated a correlation between indirect allorecognition of mismatched donor HLA Class I- and Class II-derived peptides and the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of this study was to determine whether a parallel allorecognition of mismatched donor HLA Class I- and Class II-derived peptides occurs after lung transplantation and to determine its correlation with the development of BOS after lung transplantation in a group of pediatric patients. Methods: Peripheral blood mononuclear cells from 7 BOS-positive and 6 BOS-negative pediatric lung transplant recipients (age, 11.5 ± 4.4 years) were cultured in the presence of synthetic peptides corresponding to the α-chain hypervariable regions of a mismatched donor HLA Class I molecule and the β-chain hypervariable region of a mismatched donor HLA-DR molecule. The frequencies of HLA Class I and Class II alloreactive T cells were determined using limiting dilution analysis. Results: A significant increase (p = 0.025) in HLA Class I-alloreactive T cells was observed in BOS-positive patients (7.1 × 10-5 ± 4.3 × 10-5) compared with BOS-negative patients (2.1 × 10-5 ± 1.8 × 10-6). In addition, a significant increase (p = 0.033) in HLA Class II-alloreactive T cells also was observed in BOS-positive patients (9.6 × 10-5 ± 7.9 × 10-5) compared with BOS-negative patients (1.3 × 10-5 ± 2.1 × 10-6). Conclusions: This study indicates that a parallel CD4+ T-cell alloreactivity to both donor HLA Class I and Class II molecules may play a role in the pathogenesis of BOS both in adult and pediatric lung transplant recipients.

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