Human in vitro allogeneic responses: Demonstration of three pathways of T helper cell activation

In our study, we have measured in vitro proliferation and IL-2 production by human PBL to characterize the interactions between Th cells and accessory cells (AC) involved in responses to either conventional Ag or alloantigens. IL-2 production and proliferative responses to conventional Ag, such as influenza or tetanus, are exclusively dependent on the presence of CD4⁺ T cells and AC. In contrast, IL-2 and proliferative responses to alloantigen can be mediated by either CD4⁺ or CD8⁺ T cells. CD4⁺ T cells respond to alloantigen using either autologous AC (self-restricted), or allogeneic AC (allo-restricted), whereas CD8⁺ T cells respond to alloantigen using allogeneic AC only. The understanding of Th cell-AC interactions involved in in vitro allogeneic responses will be important for delineating the Th cell-AC interactions involved in transplantation immunity as well as in clinical disorders characterized by T cell dysfunction such as human immunodeficiency virus infection and systemic lupus erythematosus.