Clonal expansion of alphabeta-T lymphocytes with inverted Jbeta1 bias in familial hemophagocytic lymphohistiocytosis.
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 alphabeta-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 beta chain (Jbeta)-PCR, a single-strand conformation polymorphism (SSCP), and sequence analysis. A high frequency (15%) of Vbeta and Valpha families was observed in 3 of 5 and 4 of 4 patients examined, respectively. In 19 Vbeta repertoires, including all highly frequent Vbeta, the Jbeta-PCR analysis showed restricted usage of the Jbeta family, indicating a marked bias to Jbeta1 subsets (the mean rate of Jbeta1:Jbeta2 was 87:13 in 65% of the alphabeta-T cells) in widespread alphabeta-T cells (in all patients but 1). In all patients, the clonality of specific Vbeta-Jbeta fragment expanded was confirmed by SSCP and sequence analysis. These results suggest that the existence of clonal expansion and restricted Jbeta1 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.
Nagano
M
M
First Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
Kimura
N
N
Ishii
E
E
Yoshida
N
N
Yoshida
T
T
Sako
M
M
Hibi
S
S
Imashuku
S
S
Miyazaki
S
S
Hara
T
T
Mizutani
S
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019674:Genes, T-Cell Receptor beta; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D018807:Polymorphism, Single-Stranded Conformational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta