CYTOTOXIC T-LYMPHOCYTE RESPONSES TO CYTOMEGALOVIRUS IN NORMAL AND SIMIAN IMMUNODEFICIENCY VIRUS-INFECTED RHESUS MACAQUES

Disseminated cytomegalovirus (CMV) infection is a frequent occurrence in human immunodeficiency virus-infected humans and in simian immunode ficiency virus (SIV)-infected rhesus macaques. Rhesus macaques are a s uitable animal model with which to study in vivo interactions between CMV and AIDS-associated retroviruses. Since cytotoxic T lymphocytes (C TL) play a major role in control of viral infections, we have characte rized CMV-specific CTL responses in SIV-infected and uninfected rhesus macaques. Autologous fibroblasts infected with rhesus CMV were used t o stimulate freshly isolated peripheral blood mononuclear cells from C MV-seropositive animals. Following in vitro stimulation, specific CTL activity against CMV-infected autologous fibroblasts was detected in C MV-seropositive but not in CMV-seronegative normal macaques. CMV-speci fic CTL activity comparable to that in normal animals was also detecte d in two CMV-seropositive macaques infected with a live attenuated SIV strain (SIV Delta 3) and in two of three macaques infected with patho genic SIV strains. The CMV-specific CTL response was class I major his tocompatibility complex restricted and mediated by CD8(+) cells. An ea rly CN protein(s) was the dominant target recognized by bulk CTL, alth ough the pattern of CTL recognition of CMV proteins varied among anima ls. Analysis of CMV-specific CTL responses in macaques should serve as a valuable model for CMV immunopathogenesis and will facilitate prosp ective in vivo studies of immune interactions between CMV and SIV in A IDS.