The T-cell receptor repertoire is strikingly similar in older nude mice compared to normal adult mice

Abstract

Due to the absence of a normal thymus, nude mice are characterized by low numbers of mature T cells. It has been shown in older nude mice that appreciable numbers of Thy-1+, CD8+ and, to a much lesser extent, CD4+ T cells can be found. A second T-cell receptor (TCR), γδ-TCR, has been shown to be expressed by a large number of T cells in young and old nude mice. Recent data suggest that certain γ and δ chain variable (V), diversity (D), joining (J) and constant (C) region genes are associated witb both temporal and spatial organization of the γδ-T-cell repertoire in normal mice. In this study we observed the predominant use of Vγ2Jγ1Cγ1 and Vδ5Jδ1Cδ in the spleen of older nude mice. In the skin, a near exclusive expression of Vγ3Jγ1Cγ1 and Vδ1Jδ2Cδ gene segments was observed. In addition, a dendritic epidermal cell (DEC) clone was isolated from the skin of a nude mouse and expressed a γδ receptor consisting of Vγ3Jγ1Cγ1 and Vδ1Jδ2Cδ. Preliminary results show that this clone kills only YAC (an NK target) and not other tumor targets. The killing can be redirected by anti-CD3 monoclonal antibody which suggests that the receptor is potentially functional. These results demonstrate that without normal thymus development nude mice not only produce γδ- T cells with a lytic potential, but also manage to express γδ-TCR's that are similar in spatial arrangement to normal mice. This suggests a possible difference in the requirements for γδ-TCR ontogeny.