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.
Vie
H
H
Institut National de la Santé et de la Recherche Médicale, Nantes, France.
Chevalier
S
S
Garand
R
R
Moisan
J P
JP
Praloran
V
V
Devilder
M C
MC
Moreau
J F
JF
Soulillou
J P
JP
D000380:Agranulocytosis / Q000503:physiopathology*; D000943:Antigens, Differentiation / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D001854:Bone Marrow Cells; D003602:Cytotoxicity, Immunologic; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D008214:Lymphocytes / Q000145:classification / Q000502:physiology*; D008875:Middle Aged; D009503:Neutropenia / Q000503:physiopathology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta
D000943:Antigens, Differentiation; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta