| Title: |
IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection |
| Authors: |
Younes, SA; Freeman, ML; Mudd, JC; Shive, CL; Reynaldi, A; Panigrahi, S; Estes, JD; Deleage, C; Lucero, C; Anderson, J; Schacker, TW; Davenport, MP; McCune, JM; Hunt, PW; Lee, SA; Serrano-Villar, S; Debernardo, RL; Jacobson, JM; Canaday, DH; Sekaly, RP; Rodriguez, B; Sieg, SF; Lederman, MM |
| Source: |
urn:ISSN:0021-9738 ; urn:ISSN:1558-8238 ; Journal of Clinical Investigation, 126, 7, 2745-2756 |
| Publisher Information: |
American Society for Clinical Investigation |
| Publication Year: |
2016 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
3207 Medical Microbiology; 32 Biomedical and Clinical Sciences; 3204 Immunology; Women's Health; HIV/AIDS; Clinical Research; Infectious Diseases; Immunotherapy; 2.1 Biological and endogenous factors; 6.1 Pharmaceuticals; Infection; 3 Good Health and Well Being; Adult; Aged; Animals; Anti-Retroviral Agents; Biopsy; CD8-Positive T-Lymphocytes; Case-Control Studies; Cell Proliferation; Female; Granzymes; HIV Infections; HIV-1; Haplotypes; Humans; Interleukin-15; Ki-67 Antigen; Leukocyte Common Antigens; Leukocytes |
| Description: |
In HIV-1-infected patients, increased numbers of circulating CD8 + T cells are linked to increased risk of morbidity and mortality. Here, we identified a bystander mechanism that promotes CD8 T cell activation and expansion in untreated HIV-1-infected patients. Compared with healthy controls, untreated HIV-1-infected patients have an increased population of proliferating, granzyme B + , CD8 + T cells in circulation. Vβ expression and deep sequencing of CDR3 revealed that in untreated HIV-1 infection, cycling memory CD8 T cells possess a broad T cell repertoire that reflects the repertoire of the resting population. This suggests that cycling is driven by bystander activation, rather than specific antigen exposure. Treatment of peripheral blood mononuclear cells with IL-15 induced a cycling, granzyme B + phenotype in CD8 + T cells. Moreover, elevated IL-15 expression in the lymph nodes of untreated HIV-1-infected patients correlated with circulating CD8 + T cell counts and was normalized in these patients following antiretroviral therapy. Together, these results suggest that IL-15 drives bystander activation of CD8 + T cells, which predicts disease progression in untreated HIV-1-infected patients and suggests that elevated IL-15 may also drive CD8 + T cell expansion that is linked to increased morbidity and mortality in treated patients. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
http://purl.org/au-research/grants/nhmrc/APP1080001; http://purl.org/au-research/grants/nhmrc/APP1052979; https://hdl.handle.net/1959.4/unsworks_41501; https://doi.org/10.1172/JCI85996 |
| DOI: |
10.1172/JCI85996 |
| Availability: |
https://hdl.handle.net/1959.4/unsworks_41501; https://doi.org/10.1172/JCI85996 |
| Rights: |
metadata only access ; http://purl.org/coar/access_right/c_14cb ; CC-BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.FA785CC4 |
| Database: |
BASE |