Summary  e activation of naive CD4+ and CD8+ T cells in response to antigen and their subsequent prolifera-tion and di erentiation into e ectors are important features of a cell-mediated immune response. CD4+ T cells (also known as T helper cells,  ) dif-ferentiate into several subpopulations including  1,  2,  9,  17, T and Treg cells, characterized by speci c cytokine pro les and e ector functions. However, recent evidence indicates that CD8+ T cells (termed cytotoxic T lymphocytes, CTLs or Tc cells) can di erentiate into subpopulations with similar characteristics denoted as Tc2, Tc9, Tc17 and CD8+ Treg cells in addition to CTLs. Although these sub-populations accomplish important protective func-tions, their uncontrolled responses cause immunopathology including allergy and autoimmunity. Our recent  ndings indicate a change of paradigm: dur-ing these pathologic responses, CD8+ T cell sub-populations act as strong helpers for the activity of CD4+ T cells rather than being cytotoxic. In this re-view, we focus on the role of  2,  9,  17 as well as Tc9 and Tc17 cells in asthma and auto immune en-cephalomyelitis and on their interaction during these immunopathologic responses