This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In striking contrast to Human Immunodeficiency Virus (HIV)--infected humans, natural hosts of Simian Immunodeficiency Virus do not progress to AIDS despite many years of infection. The mechanisms underlying the absence of disease progression in naturally SIV-infected monkeys are largely unknown, but their investigation will likely provide clues to the pathogenic mechanisms of HIV, which in fact originated from cross-species transmissions of SIVs.. Here we show that in SIV-infected sooty mangabeys, an African natural host species, the absence of AIDS is not related to the presence of strong and broadly reactive cellular immune responses to the virus. In fact, while SIV-specific T cells are promptly detectable in the majority of SIV-infected mangabeys, their magnitude and breadth are markedly lower than in HIV infected humans and do not correlate with either viral load or CD4+ T-cell counts. These data indicate that mechanisms other than a strong immune control underlie the disease-free co-evolution of SIV and its natural hosts.