Constitutive expression of high levels of soluble mouse CD4 in transgenic mice does not interfere with their immune function

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Abstract
Interactions of CD4 with the major histocompatibility complex (MHC) class II molecules are crucial during thymic development and subsequently for the function of single-positive CD4+CD8− T lymphocytes. Here, we have investigated the potential effects of soluble CD4 (sCD4) on the immune system. We generated two different transgenic mouse lines, which constitutively expressed either ˜100 μg/ml of monovalent or ˜20 μg/ml f decavalent mouse sCD4 molecules in their sera. Analysis of these mice revealed no differences compared to control littermates, e.g. the single-positive CD4+ cells developed normally and these cells responded to allogeneic and anti-CD3 antibody stimuli like the cells from control mice. Furthermore, the T helper cell function for antibody responses in vivo were not affected. Our data provide evidence that, in mouse, the CD4-MHC class II-interaction has very low affinity. Since sCD4 is considered to be a therapeutical agent for human immunodeficiency virus infection, these findings are not only of basic, but also of clinical interest.