CD3γ, CDδ, and CD3ζ mRNA in adult human marrow hematopoietic progenitors correlates with surface CD2 and CD7 expression

Hematopoietic stem cells from adult marrow, cord blood, or fetal liver can differentiate into myeloid and lymphoid lineages. Early steps in this differentiation process are not yet fully understood. To correlate surface antigen expression with molecular events occurring during early lymphopoietic differentiation, we examined CD3γ, CD3δ, and CD3ζ gene expression in adult human CD34⁺ marrow progenitors and their subsets. Purification by fluorescence-activated cell sorter (FACS) was used to obtain 1) a CD34⁺Lin^-DR^- population known to contain primitive, uncommitted progenitors; 2) CD34⁺/CD7⁺/CD2^-; and 3) CD34⁺/CD7⁺CD2+ cells expressing receptors associated with natural killer (NK) cell or T cell lineage commitment. We demonstrate that CD34⁺Lin^-DR^- cells do not contain CD3γ, CD3δ, or CD3ζ transcripts, consistent with the primitive uncommitted nature of progenitors in this cell population. Expression of the CD34⁺/CD7⁺/CD2^- phenotype correlates with the transcription of CD3ζ but not CD3γ or CD3δ, a pattern of transcription observed in mature blood NK but not T cells. Expression of both CD7 and CD2 on CD34⁺ cells is associated with not only CD3ζ gene transcription but also CD3γ and CD3δ, a pattern found in T cells but not mature NK cells. We have identified unique patterns of mRNA transcription in phenotypically distinct lymphoid progenitors found in the marrow. These findings raise the possibility that although primitive NK and T cell progenitors share a common differentiation pathway, divergent NK and T lineage commitment steps may occur very early in lymphopoiesis. Our findings suggest that application of in vitro marrow and thymus culture techniques may be utilized to more fully describe commitment and differentiation of early lymphoid progenitors and define the role of the microenvironment in this process.