Th1 and Th2 in human diseases.

A large body of evidence suggests the existence of functionally polarized human T cell responses based on their profile of cytokine secretion in both the CD4+ T helper (Th) and the CD8+ T cytotoxic (Tc) cell subset. Human Th1 and Th2 cells not only produce a different set of cytokines but also exhibit distinct functional properties and the preferential expression of some activation markers, such as LAG-3 and CD30, respectively. Several factors may influence Th cell differentiation into the polarized Th1 or Th2 pathway. They include the cytokine profile of "natural immunity" evoked by different offending agents, the nature of the peptide ligand, as well as the activity of some costimulatory molecules and microenvironmentally secreted hormones, in the context of different host genetic backgrounds. Strongly polarized human Th1-type and Th2-type responses not only play different roles in protection, Th1 being effective in the defense against intracellular pathogens and Th2 against intestinal nematodes, but are also responsible for different types of immunopathological reactions. Th1-dominated responses may be involved in the pathogenesis of organ-specific autoimmune disorders, acute allograft rejection, unexplained recurrent abortions, contact dermatitis, and some chronic inflammatory disorders of unknown etiology. In contrast, Th2-type responses are responsible for Omenn's syndrome, reduced protection against some intracellular pathogens, transplantation tolerance, chronic GVDH, atopic disorders, and some systemic autoimmune diseases.