Correction of Abnormal T-Cell Receptor Repertoire During
Interferon-
Therapy in Patients With Hairy Cell Leukemia
Hanneke C. Kluin-Nelemans,
Michel G.D. Kester,
Lisette van deCorput,
Patrick P.C. Boor,
Jim E. Landegent,
Jacques J.M. van Dongen,
Roel Willemze, and
J.H. Frederik Falkenburg
From the Laboratory of Experimental Hematology, Department of
Hematology, Leiden University Medical Center, Leiden; and the
Department of Immunology, Erasmus University Rotterdam, Rotterdam, The
Netherlands.
Patients with the B-cell malignancy hairy cell leukemia (HCL)
exhibit a skewed T-cell repertoire with oligoclonal expression or
absence of many members of the T-cell receptor (TCR) BV gene families.
To evaluate whether interferon-
(IFN-) therapy would not only
restore normal hematopoiesis, but also the abnormal T-cell repertoire,
we studied T lymphocytes from a cohort of HCL patients treated by
IFN- in the past, at initiation, and at several intervals up to 6 years of IFN- treatment. The junctional regions from 22 TCRBV gene
families were analyzed after polymerase chain reaction amplification of
cDNA (RT-PCR) using family specific primers. In all seven patients
improvement of the skewed T-cell repertoire was not seen until 2 years
of treatment. It consisted of disappearance of oligoclonal
subpopulations and (polyclonal) reappearance of absent TCRBV gene
families. The RT-PCR results were correlated with the TCRBV protein
expression using TCRBV-specific monoclonal antibodies. T lymphocytes
from four patients with active HCL contained large expansions of
particular TCRBV-expressing cells (up to 25% of the CD3+
cells; 600 to 700/µL whole blood), which decreased during IFN- therapy in both patients tested. Finally, restoration of the TCR repertoire matched normalization of the functional immune repertoire as
measured by proliferative, helper, and cytotoxic T-lymphocyte precursor
frequencies against major histocompatibility complex-unrelated individuals. In conclusion, oligoclonal bands of TCRBV gene families found by RT-PCR correspond with a dramatic increase in circulating T
lymphocytes expressing the same TCRBV family. Moreover, IFN- can
restore the skewed T-cell repertoire and suppress persistent T-cell
clones upon treatment of the accompanying malignancy.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4224-4231
© 1998 by The American Society of Hematology.
