Gene Rearrangements and Expression in Normal and Leukemic Large Granular Lymphocytes / Natural Killer Cells

1500 Blood, Vol 70, No 5 (November), 1987: pp 1500-1508 The large granular lymphocyte (LGL) population. which effects a natural killer (NK) function. consists of cells whose lineage derivation has not been clearly established on the basis of phenotypic and functional properties. To clarify the relationship of LGL/NK cells to T cells we studied patterns of rearrangement and expression of the T cell receptor (Ti) genes a. /9. and ‘y in normal human LGLs; in CD8 , CD8. Mol . and Mo1 IGI subsets; and in 17 cases of leukemic LGL proliferations (T”yLPD). Ta, and T. genes were not expressed. nor were T and T7 genes rearranged in normal LGLs or IGI subsets. The T. LPD were divided into two groups. One group (15/17 cases) was characterized as CD3 and displayed Ti gene rearrangements. Seven of these cases were reactive with monoclonal antibody WT31 #{149} which suggested expression of an a/fl heterodimer on the cell surface. The other group L ARGE GRANULAR LYMPHOCYTES (LGL) are the principal effectors of natural killer (NK) function and antibody-dependent cell-mediated cytotoxicity (ADCC, K cell activity). They function in vivo as effectors of natural resistance against foreign cells, certain infectious agents, and tumor cells.”2 The LGL/NK population is heterogeneous and consists of cells sharing phenotypic and functional properties with both T cells and myelomonocytic cells.”2 As a result, their precise lineage derivation and mechanisms of immune function have remained unresolved and their place in hematopoietic differentiation pathways unclear. The relationship of LGL development and function to the T cell lineage can be approached by analyzing T cell receptor gene rearrangements and expression. Two genes, T 3’4 and T 5’6 code for the complete T cell antigen receptor molecule in thymocytes and in peripheral blood T cells.7 T gene rearrangements precede Ta gene rearrangements3’8 and occur in all functional T cell subsets early during thymic differentiation.9 ” A third gene, the T gene, isolated from cytotoxic T cells is also a T cell-specific rearranging gene.’2”3 The T gene is believed to rearrange even earlier in T cell differentia-