The T cell surface molecule CD4 (L3T4 in mouse) is important in the T lymphocyte response to Ag presented in association with MHC class II molecules. To examine the role of CD4 in immune function, we expressed a soluble form of murine CD4 by deleting the transmembrane and cytoplasmic regions of the L3T4 gene and transfecting the altered gene into Chinese hamster ovary cells. The recombinant soluble mouse CD4 (smCD4) retained the native conformation of the external portion, as indicated by the binding of L3T4 mAb. In vitro, smCD4 did not inhibit class II-dependent, Ag-specific, T cell proliferation or MLR, even at concentrations 300-fold greater, on a molar basis, than that of anti-CD4 mAb. Immunization of mice with smCD4 induced a strong anti-CD4 response. These antibodies showed some binding to native cell surface CD4, indicating that immunization with smCD4 generated an anti-self response. Analysis of lymphoid cells from spleen, lymph node, and thymus of smCD4-treated mice revealed no alteration in subset phenotypes. Also, Th cell function, as measured by response to soluble Ag, was not compromised. Thus, smCD4 did not inhibit T cell activity in vitro, and the autoimmune response arising from immunization with smCD4 had no apparent consequences for normal immune function.

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