Immunodeficiency with defective T-cell response to interleukin 1.

Normal proliferation of T cells in vitro requires production of and response to the lymphokine interleukin 2 (IL-2). Optimal IL-2 production by T cells is dependent on the monokine interleukin 1 (IL-1). A 10-year-old male with recurrent infections and failure to thrive was evaluated for possible defects in the production and response to IL-1 and IL-2. The patient had normal levels of serum immunoglobulins and a normal distribution of circulating T-cell subsets. However, the in vitro proliferative response of his peripheral blood mononuclear cells (PBMC) to phytohemagglutinin was depressed (40% of normal) and the response of his PBMC to antigens was absent. Delayed hypersensitivity skin tests and in vitro response to tetanus toxoid remained absent despite repeated immunizations. Monocyte function in this patient was normal as judged by the following criteria: normal expression of Ia antigens (77% +), normal IL-1 production, and normal capacity to present tetanus toxoid to a maternal T-cell line specific for tetanus toxoid antigen. The abnormal phytohemagglutinin response of the patient's PBMC was corrected by the addition of exogenous IL-2. IL-2 production by the patient's phytohemagglutin-stimulated PBMC was severely deficient but was corrected by the addition of phorbol 12-myristate 13-acetate, suggesting a defective response to IL-1. T-cell blasts derived from a normal subject but not T-cell blasts derived from the patient absorbed out IL-1 activity from a preparation of purified human IL-1. These results indicate that the patient's T-cell deficiency was due to a defective T-cell response to IL-1 and suggest that IL-1 plays an important role in the in vivo immune response.