Human T-Cell Clones

Techniques for generating human T-cell clones (TCCs) were first described nearly two decades ago (1 , 2 ). This was a direct consequence of the discovery of T-cell growth factor and the subsequent ability to propagate T-cells over extended periods (3 ). Early on, numerous publications in immunology indicated an apparently unlimited growth potential of normal mammalian T lymphocyte cultures; however, even at this time, other investigators challenged this conclusion (4 , 5 ). Nonetheless, the possibility remained that at least some TCCs represented an exception to the rule of the Hayflick Limit for growth of normal somatic cells. If this were the case, the real relevance of replicative senescence as a universal phenomenon would be highly questionable. On the other hand, if those T-cells surviving apparently indefinitely were endowed with the properties of stem cells rather than differentiated cells, this quandary would be resolved. However, as far as could be judged, the apparently immortal TCCs described in the literature seemed to possess all the attributes of normal T-cells, not stem cells. Several explanations for this apparent paradox have been proposed, the most likely of which may be that such immortal lines are in fact abnormal. Few clones were tested for karyotypic or other abnormalities. Such analyses, when performed, often revealed genetic aberrations in human as well as murine clones (6 , 7 ). In the case of murine cells, continuous cultures often transform spontaneously in culture, but in humans this is rare or absent.