Cytotoxic T lymphocytes infiltrating the human cardiac allograft show a restriction in T-cell receptor V beta gene usage: a study on serial biopsy and blood specimens.
T lymphocytes were propagated in vitro from endomyocardial biopsy specimens that were obtained weekly from four patients during the first 2 to 3 months after heart transplantation. The culture was performed in the presence of recombinant interleukin-2 and interleukin-4, with or without mitogen, in which especially CD8+ donor-specific cytotoxic T cells expanded. These cells, presumably reflecting an in vivo activated population, could even be cultured from biopsy specimens without histopathologic signs of rejection. A preferential expression of T cell receptor V beta gene families was found in these T-cell lines. This finding is in contrast with the heterogenous expression in peripheral blood T cells of the same patient. The restriction in V beta gene family expression was substantiated in the evaluation of clones obtained from two cell lines. Among 17 donor-specific cytotoxic T-cell clones derived from one cell line, only four V beta gene families were expressed. All five clones from the other cell line used the V beta 8 family. Some clones expressing a distinct V beta gene family used the same V-D-J junction sequence, indicative of their origin from the same precursor. With the use of oligonucleotide probes complementary to clone-specific V-D-J junction sequences, four of five clones were detected not only in the parent T-cell line but also in T-cell lines derived from biopsy specimens with rejection reactions taken 1 week earlier and 2 weeks later and in blood cells taken before and 0.5, 3, and 6 months after transplantation; these clones were not detected in blood cells harvested 12 months after transplantation. This study showed a restricted usage of the V beta gene families by activated donor-specific cytotoxic T lymphocytes in the heart transplant.
Hu
H
H
Department of Pathology, University Hospital, Utrecht, The Netherlands.
de Jonge
N
N
Doornewaard
H
H
Gmelig-Meyling
F H
FH
Tilanus
M G
MG
Bosboom
K
K
Robertus
M
M
Plomp
S
S
van Reijsen
F C
FC
Laphor
J R
JR
D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D001706:Biopsy; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D004699:Endocardium / Q000473:pathology*; D006680:HLA Antigens / Q000032:analysis; D016027:Heart Transplantation; D006801:Humans; D008969:Molecular Sequence Data; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology*
D015703:Antigens, CD; D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta