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Indirect recognition of donor HLA class I peptides in lung transplant recipients with bronchiolitis obliterans syndrome.
Transplantation. 1999 Apr 27; 67(8):1094-8.T

Abstract

BACKGROUND

The presentation of donor MHC class II-derived peptides by host antigen-presenting cells in the context of self-MHC class II molecules has been suggested as a mechanism for the chronic rejection of kidney and heart allografts. The aim of this study was to determine whether indirect allorecognition of HLA class I-derived peptides occurred in lung transplant (LTx) recipients and whether it correlated with the development of bronchiolitis obliterans syndrome (BOS).

METHODS

Peripheral blood mononuclear cells from LTx recipients were cultured with synthetic peptides corresponding to the hypervariable regions of the mismatched HLA class I antigens of the donor. Proliferation and precursor frequency (PF) of allopeptide reactive T cells were determined by the incorporation of [3H]thymidine into DNA and limiting dilution analysis.

RESULTS

Peripheral blood leukocytes of LTx recipients with BOS mismatched for HLA class I molecules showed a proliferative response three- to fourfold higher than those observed in mismatched recipients without BOS and in normal control individuals (P<0.001). Similarly, the PF of allopeptide-reactive T cell was 3- to 24-fold higher in recipients with BOS compared with recipients without BOS (P<0.05) as well as normal control individuals (P<0.03). The T cell PF to donor-specific allopeptides, as well as irrelevant allopeptides, was not significantly different in LTx recipients without BOS and normal control individuals.

CONCLUSIONS

These data suggest that T cells from LTx recipients are sensitized to mismatched HLA class I antigens. The sensitization was significantly higher in LTx recipients with BOS compared with LTx recipients without BOS. Strategies to block T-cell responses generated by indirect allorecognition after lung transplantation may provide a means for the prevention or treatment of BOS in LTx recipients.

Authors+Show Affiliations

Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10232557

Citation

SivaSai, K S., et al. "Indirect Recognition of Donor HLA Class I Peptides in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome." Transplantation, vol. 67, no. 8, 1999, pp. 1094-8.
SivaSai KS, Smith MA, Poindexter NJ, et al. Indirect recognition of donor HLA class I peptides in lung transplant recipients with bronchiolitis obliterans syndrome. Transplantation. 1999;67(8):1094-8.
SivaSai, K. S., Smith, M. A., Poindexter, N. J., Sundaresan, S. R., Trulock, E. P., Lynch, J. P., Cooper, J. D., Patterson, G. A., & Mohanakumar, T. (1999). Indirect recognition of donor HLA class I peptides in lung transplant recipients with bronchiolitis obliterans syndrome. Transplantation, 67(8), 1094-8.
SivaSai KS, et al. Indirect Recognition of Donor HLA Class I Peptides in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome. Transplantation. 1999 Apr 27;67(8):1094-8. PubMed PMID: 10232557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indirect recognition of donor HLA class I peptides in lung transplant recipients with bronchiolitis obliterans syndrome. AU - SivaSai,K S, AU - Smith,M A, AU - Poindexter,N J, AU - Sundaresan,S R, AU - Trulock,E P, AU - Lynch,J P, AU - Cooper,J D, AU - Patterson,G A, AU - Mohanakumar,T, PY - 1999/5/8/pubmed PY - 1999/5/8/medline PY - 1999/5/8/entrez SP - 1094 EP - 8 JF - Transplantation JO - Transplantation VL - 67 IS - 8 N2 - BACKGROUND: The presentation of donor MHC class II-derived peptides by host antigen-presenting cells in the context of self-MHC class II molecules has been suggested as a mechanism for the chronic rejection of kidney and heart allografts. The aim of this study was to determine whether indirect allorecognition of HLA class I-derived peptides occurred in lung transplant (LTx) recipients and whether it correlated with the development of bronchiolitis obliterans syndrome (BOS). METHODS: Peripheral blood mononuclear cells from LTx recipients were cultured with synthetic peptides corresponding to the hypervariable regions of the mismatched HLA class I antigens of the donor. Proliferation and precursor frequency (PF) of allopeptide reactive T cells were determined by the incorporation of [3H]thymidine into DNA and limiting dilution analysis. RESULTS: Peripheral blood leukocytes of LTx recipients with BOS mismatched for HLA class I molecules showed a proliferative response three- to fourfold higher than those observed in mismatched recipients without BOS and in normal control individuals (P<0.001). Similarly, the PF of allopeptide-reactive T cell was 3- to 24-fold higher in recipients with BOS compared with recipients without BOS (P<0.05) as well as normal control individuals (P<0.03). The T cell PF to donor-specific allopeptides, as well as irrelevant allopeptides, was not significantly different in LTx recipients without BOS and normal control individuals. CONCLUSIONS: These data suggest that T cells from LTx recipients are sensitized to mismatched HLA class I antigens. The sensitization was significantly higher in LTx recipients with BOS compared with LTx recipients without BOS. Strategies to block T-cell responses generated by indirect allorecognition after lung transplantation may provide a means for the prevention or treatment of BOS in LTx recipients. SN - 0041-1337 UR - https://www.unboundmedicine.com/medline/citation/10232557/Indirect_recognition_of_donor_HLA_class_I_peptides_in_lung_transplant_recipients_with_bronchiolitis_obliterans_syndrome_ L2 - http://dx.doi.org/10.1097/00007890-199904270-00002 DB - PRIME DP - Unbound Medicine ER -