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.
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.
Metzger
R
R
Institute of Immunology, University of Heidelberg, München, Germany.
Heckl-Ostreicher
B
B
Nerl
C
C
Schondelmaier
S
S
Kabelitz
D
D
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007945:Leukemia, Lymphoid / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D016898:Interferon-alpha; D016692:Receptors, Antigen, T-Cell, gamma-delta