Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors

Abstract

The T-cell repertoire is elaborated by a still poorly understood process during which precursor cells arising in the bone marrow seed the thymus to provide a starting point for intrathymic differentiation and selection. The products of the process are cells which express antigen receptors composed of either α/β or γ/δ heterodimers in association with CD3 (refs 1–3). The finding that the appearance of T-cell antigen receptor γ- and δ-gene rearrangements and transcripts precedes those of full-length β- and α-transcripts during ontogeny indicates that the process is ordered^4–8, a conclusion supported by the fact that the appearance of thymocytes expressing CD3-associated γ/δ heterodimers precedes the appearance of those bearing α/β heterodimers⁹. The recent demonstrations that within the γ- and δ-loci there is ordered and sometimes transient rearrangement and expression of specific Vδ and Vγ gene segments during ontogeny^7,8,10 raised the possibility that qualitative changes in the capacity of the differentiative process to generate components of the T-cell armamentarium might occur. We have produced a monoclonal antibody that detects an epitope of the Vγ3 gene product¹⁰, a gene segment expressed only in the early fetal thymus¹¹. In this report we demonstrate that cells expressing Vγ3 are present transiently at the earliest stages of thymocyte development, preceding the appearance of cells bearing other γ/δ or α/β receptors. In the adult mouse, Vγ3 expression appears to be limited to Thy-1⁺ cells in the epidermis. These results suggest a profound programming and staging in elaboration of the components of the T-cell system during the early stages of thymocyte development in the embryo.