Induction and regulation of CD4+ T cell subsets

It is now generally accepted that CD4+ T cells can be divided into at least two distinct subsets: Th1 and Th2. Th1 cells characteristically secrete interleukin 1 (IL-2) and gamma-interferon (IFN-gamma) whereas Th2 cells produce mainly IL-4, IL-5 and IL-10. Studies from many laboratories have demonstrated that the balance between these two subsets of T cells frequently determines the outcome of infectious and autoimmune diseases. Several factors influence the preferential induction and regulation of Th1 or Th2 cells in vitro and in vivo. Mice were infected with the protozoan parasite Leishmania to show that the gene encoding a major surface glycoprotein of the parasite, delivered orally in a plasmid carried by an auxotrophic Salmonella typhimurium vaccine strain (BRD509), preferentially induced Th1 cells and protective immunity against a challenge infection. The protective effect of the vaccine was augmented by administration of BRD509 carrying the genes encoding IL-2, IFN-gamma or tumour necrosis factor alpha. Cloned mouse Th1 cells specific for malarial antigens have been used to show that nitric oxide (NO) can inhibit the production of IFN-gamma by Th1 cells. Oral delivery of antigen and selective cytokines may preferentially induce CD4+ T cell subsets. Modulation of NO synthesis may further influence this induction and sustain such selective responses leading to effective therapy.