Immunological studies of gamma delta T cells in a case of large granular lymphocyte (LGL) leukemia: leukemic gamma delta+ T cells are resistant to growth stimulation in vitro but respond to interferon-alpha treatment in vivo

Abstract

Leukemic T cells from patient BU (WBC 22,000/microliter) resembled morphologically large granular lymphocytes, and expressed a V delta 1-encoded gamma delta T-cell receptor (TCR) on their surface. Upon in vitro activation with various mitogens, IL-2-dependent V delta 1+ cell lines were only obtained if V delta 1+ cells had been positively selected on a cell sorter before culture. However, even under these conditions, the V delta 1+ IL-2-dependent cell lines showed a TCR beta and gamma gene-rearrangement different from that of the freshly isolated leukemic cell population, indicating that they were not derived from the leukemic clone. Thus, known T-cell growth factors (IL-2, IL-4, IL-7) in concert with mitogenic signals failed to induce in vitro proliferation of the V delta 1+ leukemic clone. Interestingly, the patient responded to treatment with interferon-alpha 2c (daily dose of 10(6) I.U.). After 2 1/2 years of continuous interferon treatment, the patient is in partial remission with WBC around 8000/microliter.