Clonal expansion of alpha beta-T lymphocytes with inverted J beta 1 bias in familial hemophagocytic lymphohistiocytosis

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare but fatal disea se in infancy. There are no previous reports on the clonality of T cells in FHL patients. We analyzed here the clonality of alpha beta-T cells in 5 FH L patients using an inverse reverse transcriptase-polymerase chain reaction (RT-PCR) of the T-cell receptor variable region gene (TCR V), a joining re gion gene of the beta chain (J beta)-PCR, a single-strand conformation poly morphism (SSCP), and sequence analysis. A high frequency (15%) of V beta an d V alpha families was observed in 3 of 5 and 4 of 4 patients examined, res pectively. In 19 V beta repertoires, including all highly frequent V beta, the J beta-PCR analysis showed restricted usage of the J beta family, indic ating a marked bias to J beta 1 subsets (the mean rate of J beta 1:J beta 2 was 87:73 in 65% of the alpha beta-T cells) in widespread alpha beta-T cel ls (in all patients but 1). In ail patients, the clonality of specific V be ta-J beta fragment expanded was confirmed by SSCP and sequence analysis. Th ese results suggest that the existence of clonal expansion and restricted J beta 1 usage of T cells in FHL is genetically associated with the pathogen esis and the immunodysfunction of the disease. These results help to explai n some of the abnormal functional behaviors of T cells in FHL and raise new questions regarding the mechanisms responsible for the restricted clonal d iversity. (C) 1999 by The American Society of Hematology.