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The T-cell receptor repertoires expressed by CD4+ and CD4- large granular
lymphocytes derived from the same patients suggest the persistent action of
an immune-mediated selection process
E Quiros-Roldan, A Sottini, M Gulletta, R Stellini, M Puoti, D Primi and L Imberti
Terzo Laboratorio Analisi, Spedali Civili, Brescia, Italy.
The lymphoproliferative syndrome with large granular lymphocytes (LGL) is
an heterogeneous disorder of unknown etiology. The analysis of T- cell
receptor (TCR) genes rearrangements has shown that, in most cases, the
disease is associated with clonal proliferation of CD8+CD57+ LGL. However,
the putative neoplastic nature of these expansions remains questionable
because clonal proliferations of CD8+ cells have recently been found also
in physiologic conditions. To obtain more precise information on the
mechanisms responsible for LGL expansions, we decided to compare the
molecular characteristics of TCRBV chains expressed by LGL with different
phenotype and function, but derived from the same patients. To this end, we
characterized, at the molecular level, the TCR repertoires of fractionated
T-cell populations of two unusual patients with concurrent expansions of
CD4+CD57+ and CD4-CD57+ LGL. Our results show that the dominant TCRBV
chains expressed by the different CD4+ and CD4- LGL populations were
strictly oligoclonal. However, the molecular characteristics of the
dominant V-D-J rearrangements also imply that the selection of these clones
was not due to a neoplastic event. Rather, our data suggest that these
particular LGL proliferations can be ascribed to a chronic T-cell- mediated
immune response that involves recognition by the engaged TCR of antigens
that are not necessarily presented to immune system in the classical major
histocompatibility complex-restricted pathway.
Volume 88,
Issue 6,
pp. 2133-2143,
09/15/1996
Copyright © 1996 by The American Society of Hematology
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