Studies were undertaken to study the maturation and immunoregulation of in vitro T-cell and B-cell responses in normal individuals and patients with immune deficiency diseases. Patients with the Wiskott-Aldrich syndrome (WAS) and ataxiatelangiectasia (A-T) were deficient in their ability to generate cytotoxic T cells to allogeneic major histocompatibility complex (MHC) antigens in vitro, an observation perhaps related to the increased frequency of neoplasms observed in these patients. Antibody responses by antigen-stimulated normal B cells were shown to be macrophage and T cell dependent. Normal B cells produced mostly IgG antibodies and small amounts of IgM and IgA antibodies. This observation was due to variations in the precursor frequency for the different isotypes, and each precursor was shown to be committed to the production of a single isotype of antibody molecule. Cells from patients with the WAS and A-T produced less antibody than controls, due to defects in both T cells and B cells but not monocytes. A monoclonal antibody, termed 7G7/B6, was produced which binds to the human interleukin-2 (IL-2) receptor at a site different from IL-2 and other monoclonal antibodies (anti-Tac) against the IL-2 receptor (IL-2R). Using 7G7/B6 and anti-Tac, an enzyme-linked immunosorbent assay (ELISA) was established to quantitatively measure soluble IL-2R. Using this ELISA, a released soluble form of the IL-2R was discovered in the culture supernatants of activated human cells in vitro. In addition, elevated levels of soluble IL-2R were found in the serum of certain patients with cancer and acquired immunodeficiency syndrome (AIDS). Soluble Il-2Rs may play an immunoregulatory role and the level of such receptor in the serum of certain patients may be indicative of alteration in immune reactivity in vivo.
