Studies were performed to examine the maturation and regulation of the human immune response in normal individuals and in patients with congenital and acquired immune deficiency states associated with a high frequency of cancer. The interaction of the T-cell derived lymphokine interleukin-2 with its cell membrane receptor (IL-2R) plays a pivotal role in the generation of immune responses. We have identified a soluble form of the IL-2R (sIL-2R) in the serum of normal individuals and found elevated levels of this receptor in a variety of malignancies of the lymphoreticular system. In patients with the Adult T-cell Leukemia (ATL), reductions in serum levels of sIL-2R correlated with responses to chemotherapy. In collaboration with Dr. Thomas Waldmann, this has also been shown in ATL patients receiving IL-2R directed therapies. Elevated serum levels of sIL-2R were also observed in patients with the acquired immune deficiency syndrome (AIDS) and carriers of the Human Immunodeficiency Virus type 1. Thus the measurement of sIL-2R is useful in the management of patients with immunologic activation in vivo. Another T-cell derived lymphokine, interleukin-6 (IL-6) plays a pivotal role in B-cell maturation. We have recently established an IL-6 responsive human tumor cell line which shares many features with the lymphoreticular malignancies occurring in AIDS patients. We have developed two monoclonal antibodies which react with this tumor cell line which do not react with normal resting peripheral blood mononuclear cells. These monoclonal antibodies may be useful in the diagnosis or treatment of AIDS lymphomas. We are current investigating the expression of tyrosine kinase responsible for Bruton's X-linked agammaglobulinemia, BTK, in patients with X-linked agammaglobulinemia and isolated growth hormone deficiency.
