The effect of cytomegalovirus infection on the host response to foreign and hapten-modified self histocompatibility antigens

Abstract

The effect of murine cytomegalovirus (MCMV) infection on the host's ability to respond to allogeneic or hapten-modified syngeneic histocompatibility antigens was characterized by an early suppressive phase followed by a phase of enhancement. Suppression of the potential to respond to allogeneic H-2 antigens, as measured by an in vitro cell-mediated lympholysis assay, was seen on days 2-4 postinfection with MCMV, and was greatest at larger doses of virus and in mice with H-2 haplotypes associated with genetic susceptibility to MCMV. In mice of the C57BL genetic background, such responses had returned to normal levels by day 6 and thereafter (days 7-13) the potential of the infected host to respond to allogeneic histocompatibility determinants was markedly enhanced compared with uninfected control mice. This enhancement of alloreactivity was maximal at lower doses of virus and was coincident with the emergence of reactivity to self antigens, as measured by autoantibody production. A similar pattern of time-dependent suppression and enhancement of the hapten modified self cytotoxic response was observed. Enhancement of alloreactivity during MCMV infection was dependent on the genetic constitution of the host with the response of BALB/c mice remaining in a suppressive phase for up to 17 days postinfection. The possibility that this in vitro finding of enhanced alloreactivity during MCMV infection underlies the clinical observations of association between episodes of kidney allograft rejection and cytomegalovirus infection is discussed.