Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2374-2382
Clonal Expansion of 
-T Lymphocytes With Inverted J1 Bias in
Familial Hemophagocytic Lymphohistiocytosis
Mitsuyuki Nagano,
Nobuhiro Kimura,
Eiichi Ishii,
Nobuyuki Yoshida,
Tetsuya Yoshida,
Masahiro Sako,
Shigeyoshi Hibi,
Shinsaku Imashuku,
Sumio Miyazaki,
Toshiro Hara, and
Shuki Mizutani
From the First Department of Internal Medicine, Fukuoka University
School of Medicine, Fukuoka, Japan; the Division of Pediatrics,
Hamanomachi Hospital, Fukuoka, Japan; the Department of Pediatrics,
Saga Medical School, Saga, Japan; the Division of Pediatrics, Osaka
City General Hospital, Osaka, Japan; the Department of Pediatrics,
Kyoto Prefectural University of Medicine, Kyoto, Japan; the Department
of Virology, National Children's Hospital Medical Research Center,
Tokyo, Japan; and the Department of Pediatrics, Kyushu University,
Fukuoka, Japan.
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare but
fatal disease in infancy. There are no previous reports on the
clonality of T cells in FHL patients. We analyzed here the clonality of
-T cells in 5 FHL patients using an inverse reverse transcriptase-polymerase chain reaction (RT-PCR) of the T-cell receptor
variable region gene (TCR V), a joining region gene of the chain
(J)-PCR, a single-strand conformation polymorphism (SSCP), and
sequence analysis. A high frequency (15%) of V and V families
was observed in 3 of 5 and 4 of 4 patients examined, respectively. In
19 V repertoires, including all highly frequent V, the J-PCR
analysis showed restricted usage of the J family, indicating a
marked bias to J1 subsets (the mean rate of J1:J2 was 87:13 in
65% of the -T cells) in widespread -T cells (in all
patients but 1). In all patients, the clonality of specific V-J
fragment expanded was confirmed by SSCP and sequence analysis. These
results suggest that the existence of clonal expansion and restricted
J1 usage of T cells in FHL is genetically associated with the
pathogenesis and the immunodysfunction of the disease. These results
help to explain some of the abnormal functional behaviors of T cells in
FHL and raise new questions regarding the mechanisms responsible for
the restricted clonal diversity.
