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

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 approximately 100 micrograms/ml of monovalent or approximately 20 micrograms/ml of 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.