Concomitant allorecognition of mismatched donor HLA class I- and class II-derived peptides in pediatric lung transplant recipients with bronchiolitis obliterans syndrome.
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 alpha-chain hypervariable regions of a mismatched donor HLA Class I molecule and the beta-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 x 10(-5) +/- 4.3 x 10(-5)) compared with BOS-negative patients (2.1 x 10(-5) +/- 1.8 x 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 x 10(-5) +/- 7.9 x 10(-5)) compared with BOS-negative patients (1.3 x 10(-5) +/- 2.1 x 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.
Lu
Kim C
KC
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Jaramillo
Andrés
A
Mendeloff
Eric N
EN
Huddleston
Charles B
CB
Sweet
Stuart C
SC
Patterson
G Alexander
GA
Mohanakumar
T
T
D001989:Bronchiolitis Obliterans / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D007519:Isoantigens