Lymphokine regulation and the role of abnormal regulation in immunodeficiency

T cell-derived lymphokines mediate or modulate various aspects of the immune response and immunodeficiency states related to abnormalities in lymphokine production or regulation are now being recognized. One example of this is seen in the fetus and neonate, in whom a physiologic immunodeficiency appears to reflect in part deficient production of certain lymphokines, including interferon-gamma, IL-4, and IL-5. The deficiency in production of these lymphokines appears to reflect to a large extent the paucity of memory T cells during these periods of life. Diminished lymphokine production has also recently been implicated as the cause for three cases of primary severe combined immunodeficiency. In disorders associated with excess IgE production, including allergy, hyper IgE syndrome, and Omenn's syndrome, excess IL-4 production relative to the production of interferon-gamma may play a contributory role. Regulation of the production of these and other T cell-derived lymphokines appears to be affected predominantly by control of lymphokine gene transcription, the basis for which is just now becoming understood at a molecular level. The elucidation of these regulatory mechanisms offers the promise for understanding the basis for disordered lymphokine production in immunodeficiency states.