Cytomegalovirus mediates expansion of IL-15–responsive innate-memory cells with SIV killing function
| Autor: | Dennis J. Hartigan-O'Connor, Paul A. Luciw, Hung T. Kieu, Wenze Lu, Christian Brander, Gema Méndez-Lagares, Jaewon Lee, W. L. William Chang, Peter A. Barry, Sung Jin Kim, Lourdes Adamson, Miriam Rosás-Umbert, David E. Merriam, Ning Chin |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Simian Acquired Immunodeficiency Syndrome Cytomegalovirus CD8-Positive T-Lymphocytes Biology 03 medical and health sciences 0302 clinical medicine Immune system Animals Antigen-presenting cell Interleukin-15 Innate immune system General Medicine Macaca mulatta Virology Immunity Innate Killer Cells Natural 030104 developmental biology Interleukin 15 030220 oncology & carcinogenesis Female Simian Immunodeficiency Virus Clone (B-cell biology) Immunologic Memory CD8 Ex vivo Research Article K562 cells |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 |
| DOI: | 10.1172/jci148542 |
| Popis: | Interindividual immune variability is driven predominantly by environmental factors, including exposure to chronic infectious agents such as cytomegalovirus (CMV). We investigated the effects of rhesus CMV (RhCMV) on composition and function of the immune system in young macaques. Within months of infection, RhCMV was associated with impressive changes in antigen presenting cells, T cells, and NK cells—and marked expansion of innate-memory CD8(+) T cells. These cells express high levels of NKG2A/C and the IL-2 and IL-15 receptor beta chain, CD122. IL-15 was sufficient to drive differentiation of the cells in vitro and in vivo. Expanded NKG2A/C(+)CD122(+)CD8(+) T cells in RhCMV-infected macaques, but not their NKG2-negative counterparts, were endowed with cytotoxicity against class I–deficient K562 targets and prompt IFN-γ production in response to stimulation with IL-12 and IL-18. Because RhCMV clone 68-1 forms the viral backbone of RhCMV-vectored SIV vaccines, we also investigated immune changes following administration of RhCMV 68-1–vectored SIV vaccines. These vaccines led to impressive expansion of NKG2A/C(+)CD8(+) T cells with capacity to inhibit SIV replication ex vivo. Thus, CMV infection and CMV-vectored vaccination drive expansion of functional innate-like CD8 cells via host IL-15 production, suggesting that innate-memory expansion could be achieved by other vaccine platforms expressing IL-15. |
| Databáze: | OpenAIRE |
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