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Phenotypic differences between healthy effector CTL and leukemic LGL cells support the notion of antigen‐triggered clonal transformation in T‐LGL leukemia
Author(s) -
Wlodarski Marcin W.,
Nearman Zachary,
Jankowska Anna,
Babel Nina,
Powers Jennifer,
Leahy Patrick,
Volk HansDieter,
Maciejewski Jaroslaw P.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0107073
Subject(s) - biology , ctl* , immunology , cd8 , immune system , antigen , perforin , t cell , virology
T cell large granular lymphocyte leukemia (T‐LGL) is a chronic clonal lymphoproliferation of CTL. In many ways, T‐LGL clones resemble terminal effector CTL, including down‐modulation of CD28 and overexpression of perforin, granzymes, and CD57. We studied the transcriptome of T‐LGL clones and compared it with healthy CD8+CD57+ effector cells as well as CD8+CD57– populations. T‐LGL clones were sorted based on their TCR variable β‐chain restriction, and controls were obtained by pooling cell populations from 14 donors. Here, we focus our analysis on immunological networks, as immune mechanisms play a prominent role in the etiology of bone marrow failure in T‐LGL. Informative genes identified by expression arrays were studied further in an independent cohort of patients using Taqman PCR, ELISA assays, and FACS analysis. Despite a strikingly similar gene expression profile between T‐LGL clones and their healthy counterparts, important phenotypic differences were identified, including up‐modulation of TNFRS9, myeloid cell leukemia sequence 1, IFN‐γ, and IFN‐γ‐related genes, and several integrins/adhesion molecules. In addition, T‐LGL clones were characterized by an overexpression of chemokines and chemokine receptors that are typically associated with viral infections (CXCL2, Hepatitis A virus cellular receptor 1, IL‐18, CCR2). Our studies suggest that immunodominant LGL clones, although phenotypically similar to effector CTL, show significantly altered expression of a number of genes, including those associated with an ongoing viral infection or chronic, antigen‐driven immune response.