A hole in the T-cell repertoire induced after retroviral infection of immunocompetent adult mice

Abstract

Background Acute virus infections resolve following the establishment of host immune responses, and this is also true for infections with most simple retroviruses. Thus, inoculation into neonates and the resultant induction of immune tolerance are required for the development of murine gammaretrovirus-induced leukemia/lymphoma. On the other hand, most complex retroviruses establish persistent infection in immunocompetent adult animals and induce pathologies after a prolonged latent period. Friend virus (FV) composed of two simple gammaretroviruses, replication-competent Friend murine leukemia virus (F-MuLV) and acutely growth-inducing but defective spleen focus-forming virus, is a prominent exception to the above general rules and can induce a rapid development of fatal leukemia when inoculated into immunocompetent adult mice of susceptible strains [1]. Virus antigen-reactive CD8 cells undergo an unusually rapid process of exhaustion in the presence of massively expanding FV-infected cells [2], resulting in profound failure in maintaining FV-specific memory T cells. However, even when acute splenomegaly is resolved in resistant animals, they cannot reject FV-induced leukemia cells and die after tumor cell injection, suggesting that FV-infected mice fail to generate virus antigen-specific naive T cells.