EXPRESSION OF THE ZETA-PROTEIN SUBUNIT IN CD3(-) NK EFFECTORS DERIVEDFROM HUMAN THYMUS

The origin, lineage derivation, and sites of human natural killer (NK) cell differentiation are presently unresolved. The vast majority of N K cells found in peripheral blood have surface membrane expression of CD2 and CD16. Both antigens trigger activation pathways which require the zeta protein, a signal-transducing subunit of the CD3-T cell recep tor (CD3-TCR) complex which is found as an isolated homodimer (zeta-ze ta) or heterodimer (zeta-Fc epsilon RI gamma) in human NK cells. Unlik e NK cells found in adult peripheral blood, NK cells derived in vitro from human CD34(+) hematopoietic progenitor cells lack CD2 and CD16, a nd those found in fetal liver constitutively express CD3 epsilon and d elta proteins. However, NK effecters derived in vitro from immature hu man CD3(-) thymocytes show striking phenotypic and functional similari ties to adult human NK cells. In this report, we characterize zeta pro tein expression in CD3(-) thymocytes following short-term culture in r ecombinant (r)IL-2. CD3(-)CD56(+) thymocyte NK effecters express the z eta protein as a disulphide-linked homodimer of 32 kDa, yet lack other protein components of the CD3-TCR complex. Both CD16(+) and CD16(-) p opulations were found to express zeta, and within the CD16(+) fraction , zeta is physically associated with CD16. These data provide evidence of additional similarities between adult peripheral blood NK cells an d CD3(-)CD56(+) NK effectors derived from human thymocytes, and sugges t that under these experimental conditions, human NK cells can arise f rom early thymic precursors. (C) 1994 Academic Press, Inc.