Long-term cultivation and productive infection of primary thymocyte cultures by a thymocytopathic murine retrovirus

ts1, a mutant of MoMuLV, selectively kills T cells and neurons in the infected host resulting in neuroimmunodegeneration. In the infected thymus there is an early increase in mitosis of thymocytes followed by rapid death, suggesting that thymocyte death may be induced by viral mitogenic activation. Studies on thymocytes obtained from ts1-infected mice indicated that the ts1-induced depletion of thymocytes is mediated through activation-induced death by apoptosis. To further investigate the interaction between ts1 and thymocytes, we have established long-term primary murine thymocyte cultures by placing the thymocytes together with thymic remnants in culture medium containing IL-2 and IL-7. These thymocytes retained their immature phenotype and we susceptible to infection by ts1 and its parental wild-type MoMuLV. ts1-infected thymocytes proliferated initially at accelerated rate but subsequently produced more infectious virus and died much faster than control or MoMuLV-infected thymocytes. These in vitro studies to some extent reflect our in vivo studies reported previously.