The finite life span of human T lymphocytes and their requirement of regular restimulation frequently limit human T cell studies. Once infected with H. saimiri, however, human and monkey T cells are transformed to stable growth without the need for further restimulation. H. saimiri persists in human growth-transformed T cells episomally and only a few viral genes are expressed. The release of infectious virus from transformed human T cells has not been observed. H. saimiri-transformed T cells have the phenotype of mature activated CD4+ or CD8+ T cells. Transformed T cells retain a structurally and functionally intact T cell receptor and respond specifically to recognition of their antigen. They produce Th1-like cytokines, provide B cell help, can be triggered to become cytotoxic, and are sensitive to a variety of apoptosis-inducing treatments. While H. saimiri-transformed T cells resemble native T cells in numerous aspects, their reactivity to CD2 is strikingly different: Native T cells are activated via CD2 by certain pairs of mAbs, but not by the mere binding of CD2 to its ligand CD58. In contrast, H. saimiri-transformed T cells are activated by a single crosslinked anti-CD2 mAb and also by interaction with CD58-bearing cells.