SIV Replication in the Infected Rhesus Macaque Is Limited by the Size of the Preexisting T H 17 Cell Compartment
Year: 2012
Type: article
Abstract: 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 (T(H)17) 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 T(H)17 cells. Reciprocally, treatment of macaques with interleukin-2 and granulocyte colony-stimulating factor before infection led to depletion of T(H)17 cells, reduction of the ratio between T(H)17 cells and CD3(+)CD4(+)CD25(+)CD127(low) 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.
Source: Science Translational Medicine
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Bill and Melinda Gates Foundation, National Institutes of Health, U.S. Public Health Service, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental and Craniofacial Research, National Center for Research Resources, California National Primate Research Center
Awards: California National Primate Research Center, G112357824, G1361149278, Role of type I interferons in mucosal anti-SIV immunity, G1473953553, G2306855594, G2436753102, G2687403502, G3250837977, Regulatory T cell influence on infant and adult immune responses to HIV, G4146859829, G9000008089, G9000050168, G9000157836, G9000193691, G9000222485, Training Program in Pediatric Gastroenterology/Nutrition, G97119092
OpenAlex ID: W2003152924