TY - JOUR
T1 - T-cell receptor gene rearrangement in T-cell large granular leukocyte leukemia
T2 - Preferential Vα but diverse Jα usage in one of five patients
AU - Kasten-Sportès, Claude
AU - Zaknoen, Sara
AU - Steis, Ronald G.
AU - Chan, Wing C.
AU - Winton, Elliott F.
AU - Waldmann, Thomas A.
PY - 1994/2/1
Y1 - 1994/2/1
N2 - T-γ lymphoproliferative disease (T-γ LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T-cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T- cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR α- and β- chain genes in patients with T-γ LPD, we cloned and sequenced TCR α- and β-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common Vα nor a common Jα segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the β chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common Vα (Vα19.1). In contrast to this common Vα usage, there was a marked diversity of the Jα segments and N-region addition that were associated with the Vα19.1 segment. This pattern of common Vα usage associated with different N and Jα segments suggests an immune-mediated selection process affecting the TCR α chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR α chain and that this autoreactivity might be implicated in this patient's anemia.
AB - T-γ lymphoproliferative disease (T-γ LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T-cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T- cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR α- and β- chain genes in patients with T-γ LPD, we cloned and sequenced TCR α- and β-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common Vα nor a common Jα segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the β chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common Vα (Vα19.1). In contrast to this common Vα usage, there was a marked diversity of the Jα segments and N-region addition that were associated with the Vα19.1 segment. This pattern of common Vα usage associated with different N and Jα segments suggests an immune-mediated selection process affecting the TCR α chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR α chain and that this autoreactivity might be implicated in this patient's anemia.
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U2 - 10.1182/blood.v83.3.767.bloodjournal833767
DO - 10.1182/blood.v83.3.767.bloodjournal833767
M3 - Article
C2 - 8298138
AN - SCOPUS:0028040029
SN - 0006-4971
VL - 83
SP - 767
EP - 775
JO - Blood
JF - Blood
IS - 3
ER -