Selection of peripheral and intestinal T lymphocytes lacking CD3 ζ
Simpson S., Holländer G., She J., Levelt C., Huang M., Terhorst C., Kearney J.
The CD3 ζ chain of the TCR plays a pivotal role in the activation of T cell responses toward foreign antigen and in the selection of the T cell repertoire. T lymphocytes from mice deficient in CD3 ζ (CD3ζ/η-/- mice) express very few cell surface TCR-CD3 complexes, and these animals have poorly developed thymuses which lack single-positive CD8 and CD4 thymocytes. Nevertheless, a substantial number of single-positive CD4+ and CD8+ T lymphocytes are found in peripheral lymphold organs of CD3ζ/η/ animals. Using double-mutant mice, generated by breeding CD3ζ/η/ mice with others deficient in the expression of either class I or class II MHC molecules, we demonstrate here that positive selection of peripheral CD4+ and CD8+ T lymphocytes can occur in the absence of CD3ζ/η molecules. Analysis of the intestinal intra-eplthelial lymphocytes from CD3ζ/η/ mice revealed a novel T cell population expressing high levels of an alternative TCR αβ, due to the replacement of CD3 ζ, by FcεRlγ+. Developmentally, these cells also depend on class I MHC expression. In contrast, TCRγδ/FcεRlγ+ T cells develop Independently of MHC class I or class II molecules. These experiments demonstrate that the unique subset of intestinal TCRαβ/FcεRlγ+ lymphocytes is developmentally dependent on MHC expression. The restricted expression of TCRαβ/FcεRlγ+ cells In the Intestinal mucosa (rather than the thymus or lymph nodes) supports the hypothesis that selection of these T cells occurs extrathymlcally. © 1995 Oxford University Press.