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 alpha/beta or gamma/delta heterodimers in association with CD3. The finding that the appearance of T-cell antigen receptor gamma- and delta-gene rearrangements and transcripts precedes those of full-length beta- and alpha-transcripts during ontogeny indicates that the process is ordered, a conclusion supported by the fact that the appearance of thymocytes expressing CD3-associated gamma/delta heterodimers precedes the appearance of those bearing alpha/beta heterodimers. The recent demonstrations that within the gamma- and delta-loci there is ordered and sometimes transient rearrangement and expression of specific V delta and V gamma gene segments during ontogeny 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 V gamma 3 gene product, a gene segment expressed only in the early fetal thymus. In this report we demonstrate that cells expressing V gamma 3 are present transiently at the earliest stages of thymocyte development, preceding the appearance of cells bearing other gamma/delta or alpha/beta receptors. In the adult mouse, V gamma 3 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.