Treatment of idiopathic CD4 T lymphocytopenia with IL-2

Abstract

Idiopathic CD4 T lymphocytopenia (ICL) is an unusual immune defect in which there is an unexplained deficit of CD4 T cells, leading to fungal, parasitic or other serious opportunistic infections. Current treatment efforts are directed at eliminating infections. Here we describe the use of a novel treatment, subcutaneous polyethylene glycol (PEG)-IL-2 injections, in a woman with this disorder, who had chronic severe mycobacterial disease which led to repeated hospitalizations, and advancing respiratory insufficiency. For this patient, PEG-IL-2, 50 000 U/m2, has been given by weekly subcutaneous injections for 5.5 years. This treatment has resulted in marked (and still continuing) long-term immunological improvement with normalized T cell functions and increased CD4 cell numbers. She has had substantial clinical improvement with clearing of mycobacterial disease, reducing hospitalizations and improved lung functions. The improvement seen in this patient suggests that low-dose IL-2 is a safe and practical therapy, which might be useful in other subjects with this potentially serious immune defect.

Fig. 1

The absolute number of CD4 T cells and the ratio of CD4/CD8 cells during the period of study is given in the top two panels. The normal absolute number of CD4 cells would be 500–1700 cells/mm³ or greater, since April 1994 the absolute number of CD4 cells has been > 100/mm³, as indicated. In the lower panel the number of B cells (CD19) is given at the indicated time points. Normal B cell numbers of would be 75–375 cells/mm³. Two short courses of IFN-γ were given in 1989 and 1990; since April 1993 the patient has received IL-2 as indicated.

Fig. 2

Lymphocyte proliferative responses to the mitogens phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) were determined at intervals after starting IL-2. The results are given as ct/min of ³H-thymidine incorporation (top panel). For normal subjects, lymphocyte proliferation to PHA would be 20 000–90 000 ct/min, for Con A 7500–45 000 ct/min, and for PWM it would be 2500–30 000 ct/min. Similarly, lymphocytes were tested for proliferative responses to the antigens candida and tetanus toxoid (lower panel). These results are expressed as the stimulation index (SI), which is the number of counts for the test wells containing the antigen/the number of counts in test wells that contained no antigen. Normal subjects with positive lymphocyte responses would have SIs of ≥ 4.0 (as shown in the figure).