Correction of secondary T-cell immunodeficiencies with biological substances and drugs.

Secondary T-lymphocyte deficiencies are common in cancer, aging, malnutrition, chronic infection, and AIDS. Reconstitution with thymic hormones has not been successful. The various thymic hormone preparations induce prothymocyte differentiation and promote the differentiated functions of mature T cells, but they do not regulate intrathymic maturation. In contrast, interleukin 2, endotoxin, thymic epithelial cell products, but not interleukin 1 were found to promote functional maturation of immature thymocytes. Logically, thymic hormones may have synergistic interaction with inducers of intrathymic maturation, and preliminary evidence in athymic nude mice supports this notion. Two classes of drugs show thymomimetic actions. Levamisole, diethyl dithiocarbamate, and other sulfur-containing compounds restore T-cell function via induction of a thymic hormone-like factor. Isoprinosine, NPT 15392, and related hypoxanthine derivatives induce T-cell maturation directly and promote T-cell function in vitro and in vivo. An assessment of the combined actions of these drugs and biologicals should improve immunorestoration in T-cell deficiencies.