THE T-CELL RECEPTOR REPERTOIRES EXPRESSED BY CD4(-) LARGE GRANULAR LYMPHOCYTES DERIVED FROM THE SAME PATIENTS SUGGEST THE PERSISTENT ACTIONOF AN IMMUNE-MEDIATED SELECTION PROCESS() AND CD4()

The lymphoproliferative syndrome with large granular lymphocytes (LGL) is an heterogeneous disorder of unknown etiology. The analysis of T-c ell 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 remai ns questionable because clonal proliferations of CD8(+) cells have rec ently been found also in physiologic conditions. To obtain more precis e information on the mechanisms responsible for LGL expansions, we dec ided to compare the molecular characteristics of TCRBV chains expresse d by LGL with different phenotype and function, but derived from the S ame patients. To this end, we characterized, at the molecular level, t he TCR repertoires of fractionated T-cell populations of two unusual p atients 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 rearrang ements also imply that the selection of these clones was not due to a neoplastic event. Rather, our data suggest that these particular LGL p roliferations can be ascribed to a chronic T-cell-mediated immune resp onse that involves recognition by the engaged TCR of antigens that are not necessarily presented to immune system in the classical major his tocompatibility complex-restricted pathway. (C) 1996 by The American S ociety of Hematology.