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Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-04-1044.
Submitted April 4, 2003
Accepted June 8, 2003
Profound loss of T cell receptor repertoire complexity in cutaneous T cell lymphoma
Nikhil Yawalker, Katalin Ferenczi, David A Jones, Keiichi Yamanaka, Ki-Young Suh, Sarah Sadat, and Thomas S Kupper*
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA
* Corresponding author; email: tskupper{at}rics.bwh.harvard.edu.
Cutaneous T Cell Lymphoma is a malignancy of skin homing T cells. A major feature of CTCL is profound immunosuppression, such that patients with advanced mycosis fungoides or Sezary syndrome have been compared to patients with advanced HIV disease, and are susceptible to opportunistic infection. The etiology of this immunosuppression is unclear. We analyzed peripheral blood T cells of CTCL patients with Stage I-IV disease, using a sensitive beta-variable complementarity-determining region 3 spectratyping approach. Our data revealed a profound disruption of the complexity of the T cell repertoire, which was universally observed in patients with advanced disease (stage III and IV), and present in up to 50% of patients with early stage disease (stage I and II). In most patients, multiple monoclonal and oligoclonal CDR3 spectratype patterns in many different beta-variable families were seen. Equally striking was a reduction of normal T cells (as judged by absolute CD4 counts) across multiple beta-variable families. In general, CTCL spectratypes were reminiscient of advanced HIV spectratypes published elsewhere. Taken together, the data are most consistent with a global assault on the T cell repertoire in patients with CTCL, a process that can be observed even in early state disease.
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