THE EFFECTS OF PASSIVE ANTIVIRAL IMMUNOTHERAPY IN AKR MICE .1. THE SUSCEPTIBILITY OF AKR MICE TO SPONTANEOUS AND INDUCED T-CELL LYMPHOMAGENESIS

The AKR inbred mouse strain displays a high incidence of spontaneous T cell lymphomas that arise predominantly in the thymus of 6 to 12-mont h-old mice. Heterogenous nonacute transforming retroviruses are associ ated with the etiology of the disease: the endogenous ecotropic viruse s (inherited in AKR mice at two non-linked chromosomal loci, Akv-1 and Akv-2), the xenotropic virus acid recombinant viruses. Prevention of spontaneous T cell lymphomagenesis in AKR mice by passive anti-viral i mmunotherapy was accomplished by suppressing endogenous ecotropic viru s release. Treatment with monoclonal antibody Hy-72 reacting only with Akv1 type ecotropic viruses, or with mAb 18-5 with specificity for bo th ecotropic and MCF recombinant virus envelope glycoprotein (administ ered from birth for 10 days) inhibited similarly T cell lymphoma devel opment. A reduced thymus cellularity observed in these mAb treated mic e coincided with reduced level of earliest intrathymic low CD4 precurs or population in their thymus. The role of endogenous viruses (MuLV) a nd presence of potential lymphoma cells (PLCs) (identified among bone marrow cells of untreated AKR mice) in enhanced T cell lymphomagenesis in AKR mice, triggered by different leukemogenic agents, was evaluate d. Intrathymic injection of the radiation leukemia virus variant A-Rad LV or administration of methylnitrosourea resulted in a high lymphoma incidence within a short latent period of 80-100 days irrespective of the presence or absence of MuLV or PLCs in these treated mice. Thus, a direct action of these agents on thymocytes seems to occur. The high susceptibility of untreated AKR mice to radiation induced T cell lymph omagenesis was not affected by pretreatment with mAb Hy-72; in contras t to markedly reduced sensitivity following pretreatment with mAb 18-5 (15 vs 100%). The mAb 18-5 induced resistance to radiation lymphomage nesis seems to be related to defects in the bone marrow stem cell pool as well as in the thymus microenvironment of mAb 18-5 treated mice. T hus, different developmental pathways are involved in enhanced T cell lymphomagenesis in AKR mice.