Differential thymus dependence of rat CD8 isoform expression

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Abstract
Expression of the rat CD8 molecule was studied using five novel monoclonal antibodies (mAb), four of which are specific for the V‐like domain of CD8α, whereas one reacts either with the β chain or with a determinant only expressed on the CD8 α/β heterodimer. mAb to both chains effectively blocked purified lymph node CD8 T cells in mixed lymphocyte reaction and in cell‐mediated cytotoxicity. Flow cytometric analysis showed that CD8 T cells from lymph nodes or spleen of normal rats almost exclusively express the α/β isoform, regardless of the T cell receptor isotype (α/β or γ/δ). In contrast, natural killer (NK) cells carry only CD8α chains. This CD8α+β− phenotype was also prominent among CD8 T cells from athymic rats and from intestinal epithelium of normal rats. CD8α homodimers can also be expressed as a result of activation, as shown by analysis of CD4 CD8 double‐positive T cells obtained from highly purified lymph node CD4 T cells by in vitrok stimulation. Such CD4+CD8α+β− cells also represent a major subset among adult intestinal intraepithelial lymphocytes (IEL), suggesting local activation. Taken together, the difference in CD8 isoform expression among T cells from athymic rats, NK cells, and gut IEL versus CD8 T cells from peripheral lymphatic organs of euthymic animals suggests that like in mice, expression of the CD8 heterodimer is more dependent on intrathymic maturation than that of the homodimer. Since the more stringent thymus dependence of CD8α+β+ T cells may be due to a requirement for thymic selection on self major histocompatibility complex class I antigens, the virtually exclusive CD8α+β+ phenotype of peripheral rat γ/δ T cells could mean that antigen recognition by this subset is also restricted by MHC class I molecules.

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