Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder

Repeated analysis of peripheral blood lymphocytes (PBLs) from a patient with large granular lymphocytosis, neutropenia, and rheumatoid arthritis revealed that approximately 45% of PBLs displayed the following phenotype: CD3+, CD4-, CD8-, CD16+, HNK-1-, WT31-. This population was purified for further analysis by depletion with anti-CD4 and anti-CD8 monoclonal antibodies (MoAbs). Southern blot analysis showed preferential rearrangements of the V gamma 9 genes. Northern blot demonstrated the presence of V gamma 9 mRNA transcripts. With MoAbs directed against either the V gamma 9 peptide (Ti gamma A) or the delta chain of the gamma delta T-cell receptor (TCR delta 1), we further demonstrated that those cell surfaces expressed both V gamma 9 and a delta gene product. In addition, analysis of the gamma gene rearrangements on six clones derived from this population demonstrated a unique rearrangement on a single chromosome, strongly suggesting the monoclonality of this T-cell population. Significant cytotoxic activity against K562, U937 was observed only after an in vitro culture period with interleukin-2 (IL-2), whereas no specific inhibitory effect on autologous bone marrow (BM) CFU-G was noted.