Selective differences in the expression of the homing receptors of helper lymphocyte subsets.

Effector functions are acquired by mature CD4 T lymphocytes in an exquisitely antigen-specific and antigen-dependent fashion. T cell receptor recognition of the processed antigen presented on the major histocompatibility complex molecule by antigen-presenting cells dictates the specificity of the T cell clones that will be expanded. A complex array of further coreceptor and lymphokine-mediated interactions determines whether activation or inhibition will follow and which effector phenotype will be acquired by the lymphocytes. On the basis of a first antigen encounter, CD4 T cells are functionally defined as naive or memory/effector cells. In memory/effector T cells, the pattern of cytokine production permits further classification as Th1 or Th2 cells. Th1 cells mainly produce IFN-gamma, whereas Th2 cells mainly produce IL-4. The functional properties of these cell subsets derive from the biological activities of these (and the related) lymphokines they produce. An established body of data supports the view that the migration of T lymphocytes is distinctively different in naive and memory/effector T cells. Both CD4 and CD8 memory/effector T cells selectively migrate into nonlymphoid organs, such as the skin, the gut, and the lung through the peripheral extravascular route, whereas naive T cells migrate through the high endothelial venules and enter lymphoid tissues, such as lymph nodes, Peyers' patches, and tonsils. Furthermore, the acquisition of a Th1 or Th2 profile further implies the coordinated expression of a relatively selective array of receptors capable of rerouting them differentially. These events have a dramatic effect on the outcome of an immune response and determine whether it will be protective or not. New therapeutic strategies can be envisaged that interfere with the key molecular processes taking place during these coordinated differentiation events.