Progression to development of lymphoma in the thymus of AKR mice treated neonatally with SL 3-3 virus.

All AKR mice develop thymic lymphoma between 60 and 90 days of age after neonatal treatment with the oncogenic retrovirus SL 3-3. At 40-50 days of age, in the normal-sized thymus of virus-treated mice, cells appear that produce lymphoma when inoculated intrathymically but not when inoculated s.c. These cells are designated as thymus-dependent (TD) lymphoma cells. TD cells progress to cells that form tumors after both intrathymic and s.c. inoculation; these are designated as thymus-independent (TI) lymphoma cells. In this report, we show that the TD and TI cells can be distinguished as two distinct cell populations. Experiments show that the TD cells reside within the immature CD4- CD8- thymocyte population of the virus-treated mice. In addition, we also show that CD4- CD8- thymocytes from SL 3-3 virus-treated mice do not mature in fetal thymic stromal rudiments. Using three-color flow cytometry to trace maturation of CD4- CD8- thymocytes after intrathymic inoculation into irradiated syngeneic hosts, disregulated thymocyte maturation of this population from virus-treated mice is demonstrated. Thus, altered maturation of and the appearance of TD lymphoma cells in, the most immature population of thymocytes appears to be a first step in a multistep process of thymic lymphomagenesis caused by SL 3-3 virus.