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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 1063-1069
Oligoclonal TCRBV Gene Usage in B-Cell Chronic Lymphocytic Leukemia:
Major Perturbations Are Preferentially Seen Within the CD4 T-Cell
Subset
Mohammad-Reza Rezvany,
Mahmood Jeddi-Tehrani,
Anders Österborg,
Eva Kimby,
Hans Wigzell, and
Håkan Mellstedt
From Immune and Gene Therapy Lab, CCK, Karolinska Hospital,
Stockholm, Sweden; the Department of Immunology, School of Public
Health, Tehran University of Medical Sciences, Tehran, Iran; the
Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm,
Sweden; the Department of Hematology, Huddinge Hospital, Huddinge,
Sweden; and Microbiology and Tumorbiology Center, Karolinska Institute,
Stockholm, Sweden.
TCRBV (T-cell receptor B variable) gene usage and CDR3 size
distribution were analyzed using reverse transcription polymerase chain
reaction (RT-PCR) to assess the T-cell repertoire of 10 patients with
B-cell chronic lymphocytic leukemia (B-CLL) and in nine age-matched
healthy control donors. When the usage of each TCRBV gene within the
CD8+ T cells of the patients was compared with that of
the controls, no statistically significant difference was noted except
for BV 6S1-3. In contrast, within the CD4+ T cells of the
CLL patients, a statistically significant overexpression for four BV
families (2, 3, 5S1, 6S1-3) was seen while an underrepresentation was
noted for five BV families (10, 11, 15, 16, 19). Based on the criterion
that a value of any BV higher than the mean + 3 standard deviation
(SD) of healthy controls indicated an overexpression, individual
patients were shown to overexpress several TCRBV genes compared with
the controls. Analyses of the CDR3 length polymorphism showed a significantly higher degree of restriction within
CD4+ and CD8+ T cells of the patients, as
compared with the corresponding control T-cell population. There was a
significant difference in the CDR3 size distribution pattern with a
more polymorphic CDR3 length pattern in the age-matched controls as
compared with CLL patients, suggesting different mechanisms driving the
T cells towards a clonal/oligoclonal TCRBV usage in patients and
controls, respectively. The results show major perturbations of T cells
in CLL patients, more frequently seen in the CD4+ T-cell
subset, indicating that nonmalignant CD4+ T cells may be
involved in the pathogenesis of CLL, but also CD8+ T cells.
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