HUMAN AUTOREACTIVE CD4(-CELL CLONES USE PERFORIN-MEDIATED OR FAS() T)FAS LIGAND-MEDIATED PATHWAYS FOR TARGET-CELL LYSIS/

It is well established that target cell lysis by MHC class I-restricte d CD8(+) T cells is an important defense mechanism during infections w ith intracellular pathogens or against tumor targets. On the other han d, little is known about the physiologic role and the mechanisms of cy totoxicity of CD4(+) MHC class II-restricted T cells. We have recently demonstrated that human autoreactive CD4(+) T cells specific for one candidate autoantigen of multiple sclerosis, myelin basic protein, can mediate cytotoxicity. In the present report, we analyze the cytolytic mechanisms employed by these cells, We show that individual T cell cl ones, regardless of their cytokine phenotype, can be noncytotoxic or l yse target cells via either perforin- or Fas/Fas ligand-mediated cytot oxicity.