Decreased T-cell receptor excision circles in cutaneous T-cell lymphoma.
OBJECTIVE
The T cell repertoire in patients with advanced cutaneous T cell lymphoma (CTCL) is significantly contracted despite the presence of relatively normal absolute numbers of T cells. We propose that many normal T cells were being lost in patients with CTCL, with the remaining normal T cells expanding clonally to fill the T cell compartment. T-cell receptor excision circles (TREC) form as a result of the initial gene rearrangement in naïve T cells. Although they are stable, they do not replicate and are subsequently diluted with the expansion of a population of T cells. Their concentration is therefore a measure of unexpanded naïve T cells relative to T cells that have undergone expansion.


METHODS
We analyzed TRECs from unfractionated peripheral blood T cells from 108 CTCL patients by quantitative PCR. In patients with obvious peripheral blood involvement, we also analyzed TRECs from clonal and nonclonal T cells.


RESULTS
We found a decrease in the number of TRECs in peripheral blood of patients with CTCL at all stages of disease, and this decrease was proportional to the loss of complexity of the T cell repertoire as measured by complementarity-determining region 3 spectratyping. In patients with leukemic CTCL and a numerically expanded clone, we also found a significantly lower-than-expected number of TRECs in the nonclonal normal T cells.


CONCLUSIONS
We hypothesize that the nonmalignant T cells have proliferated to fill the empty T cell repertoire space left by the loss of other T cells, leading to diminished TRECs and loss of T-cell receptor diversity.
Yamanaka
Kei-ichi
K
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 023115, USA.
Yawalkar
Nikhil
N
Jones
David A
DA
Hurwitz
Daniel
D
Ferenczi
Katalin
K
Eapen
Sara
S
Kupper
Thomas S
TS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000032:analysis; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell