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(Circulation. 2000;101:2405.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Significant Frequencies of T Cells With Indirect Anti-Donor Specificity in Heart Graft Recipients With Chronic Rejection

Philip I. Hornick, BSc, FRCS; Philip D. Mason, PhD, FRCP; Richard J. Baker, MA, MRCP; Maria Hernandez-Fuentes, MD, PhD; Loredana Frasca, MD; Giovanna Lombardi, PhD; Kenneth Taylor, MD, FRCS; Ling Weng, MSc; Marlene L. Rose, PhD; Magdi H. Yacoub, FRCS; Richard Batchelor, MD, FRCPath; Robert I. Lechler, PhD, FRCP, FRCPath

From the Departments of Immunology (P.I.H., P.D.M., R.J.B., M.H.-F., L.F., G.L., L.W., R.B., R.I.L.) and Cardiothoracic Surgery (P.I.H., K.T.), Imperial College School of Medicine, Hammersmith Hospital, London, and Department of Cardiothoracic Surgery (M.L.R., M.H.Y.), Harefield Hospital, Middlesex, UK.

Correspondence to Philip Hornick, Department of Cardiothoracic Surgery, Imperial College School of Medicine, Du Cane Road, Hammersmith Hospital, London W12 ONN, UK. E-mail philhrnck{at}aol.com

Background—The purpose of this study was to determine whether T cells with indirect allospecificity could be detected in heart transplant recipients with chronic rejection.

Methods and Results—Human T-cell clones were used to determine the most effective way to deliver major histocompatibility complex alloantigens for indirect presentation. Seven allograft recipients with evidence of progressive, chronic rejection were selected. Four heart graft recipients with no evidence of chronic rejection were used as controls. Peripheral blood T cells and antigen-presenting cells from the recipients were cultured with frozen/thawed stored donor cells or major histocompatibility complex class I–derived synthetic peptides in limiting dilution cultures and then compared with controls using tetanus toxoid and frozen/thawed third-party cells with no human leukocyte antigens in common with the donor. In 5 of 7 patients analyzed who had chronic rejection, elevated frequencies of T cells with indirect, anti-donor specificity (iHTLf) were detected. No such elevated iHTLf were detected in recipients without chronic rejection.

Discussion—iHTLf can be obtained from human transplant recipients, which supports the contention that the indirect pathway is involved in chronic transplant rejection.

Key Words: transplantation • immunology • rejection • immune system • lymphocytes

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