Clonal expansion of γδ-T lymphocytes in an HTLV-I carrier, associated with chronic neutropenia and rheumatoid arthritis

We report on an HTLV-I carrier showing clonal proliferation of gamma delta-T lymphocytes associated with chronic neutropenia and rheumatoid arthritis (RA). A 75-year-old Japanese woman had a 20-year history of RA and was found to have neutropenia and lymphocytosis by routine examinations. Her white cell count was 5,800/mu l with 89% lymphocytes. The proliferating gamma delta-lymphocytes did not show the typical morphology of large granular lymphocytes (LGL) and were positive for CD3, TCR delta 1, and HLA-DR but negative for CD4, CD8, and delta TCS1. Clonally rearranged TCR gamma-chain (J gamma) and TCR beta-chain (C beta 1) genes were detected by Southern blot analysis. Clonality of these proliferating gamma delta-T cells was confirmed by CDR3 size analysis for the TCR delta-chain. Anti-HTLV-I antibody was positive and the pX region of HTLV-I proviral DNA was detected by PCR analysis, but clonal integration of HTLV-I proviral DNA was not detected by Southern blotting analysis. The patient's clinical course has been stable, except for infrequent infectious episodes. The association of HTLV-I/II infection with T-LGL leukemia has been reported by several groups, although most cases exhibit TCR alpha beta+ type T cells. Analysis of the junctional sequence of TCR on T-LGL leukemia cells may clarify the role of HTLV-I/II infection in clonal T-cell proliferation.