Strategies of immune reconstitution: Effects of lymphokines on murine T cell development in vitro and in vivo

Need for more effective treatment to reconstitute T cell immunity in secondary immunodeficiencies like AIDS prompted an exploration into the roles played by leukocyte products on the ontogeny of murine T lymphocytes in vitro and in vivo. It was observed that mixed lymphokines potently stimulate the proliferation of prothymocytes, immature cortical thymocytes, and mature medullary thymocytes. The effect of the natural, mixed lymphokines could be reproduced in the main by the combination of recombinant interleukin I and II. Mixed lymphokines administered in vivo augmented splenic lymphoproliferative responses in athymic nude mice without T cell marker (Thy 1.2) induction and, in neonatal mice, induced both Thy 1.2 and proliferative responses. Recombinant IL-2 at equivalent dose was less active in nude mice and not active in neonatal mice. The evidence indicates that lymphokines, particularly IL-1 and IL-2 in combination, regulate T cell ontogeny and can act in an endocrine fashion to promote T cell development in T cell-free mice having a functional thymus. Mixed lymphokines may be useful for immune reconstitution in AIDS, however, only if given prior to thymic destruction.