SIV Replication in the Infected Rhesus Macaque Is Limited by the Size of the Preexisting TH17 Cell Compartment

Macaques with abundant TH17 cells in blood and intestinal tissue before infection are resistant to SIV replication. Contextual Cues Every person’s immune system is unique—shaped by a combination of genetics and environmental insults such as the flu or food poisoning. An individual’s immunological ecosystem evolves over time, and the immune response to a particular organism may vary depending on the current status of the system. For example, some HIV-infected individuals display a rapid decline in immune health in the absence of treatment, whereas others resist disease progression. Discovering which factors contribute to these divergent responses may help to identify new ways to control, and perhaps eradicate, this disease. A logical place to look for such defining factors is among the many components of the primate immune system. Hartigan-O’Connor et al. find in macaques that the size of a particular T cell population before infection may influence simian immunodeficiency virus (SIV) replication. The authors first measured in macaques the size of a population of proinflammatory T cells—T helper 17 (TH17) cells—and found that animals with larger TH17 cell populations before SIV infection had lower peak and set-point viral loads. Moreover, depleting TH17 cells—and thus changing the ratio between TH17 cells and regulatory T cells—resulted in higher viral set points 6 months after SIV infection. Therefore, the preexisting state of the host immune system has a direct effect on the relative success of SIV infection. These observations suggest that intricate dissection of individual immunological ecosystems may help to explain the variability of HIV progression in patients. The mechanisms by which some HIV-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. Viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. However, it has been difficult to identify host immune functions that may be present before infection and that allow resistance to lentiviral disease progression. Here, we show that simian immunodeficiency virus replication in the infected rhesus macaque is limited by the size of the preexisting T helper 17 (TH17) cell compartment: Animals with a high representation of such cells in blood and intestinal tissue before infection experienced peak and set-point viral loads about one log unit lower than those with a lower representation of TH17 cells. Reciprocally, treatment of macaques with interleukin-2 and granulocyte colony-stimulating factor before infection led to depletion of TH17 cells, reduction of the ratio between TH17 cells and CD3+CD4+CD25+CD127low regulatory T cells, and higher viral loads for 6 months after infection. These results demonstrate that the composition of the host immune system before infection has an influence on the course of disease after infection. Furthermore, to the extent that this influence shapes and interacts with T cell–mediated responses to virus, our findings provide a new framework for understanding interindividual variation in responses to therapies and vaccines against HIV.