Abstract:
:Functional defects in cytotoxic CD8(+) T cell responses arise in chronic human viral infections, but the mechanisms involved are not well understood. In mice, CD4 cell-mediated interleukin-21 (IL-21) production is necessary for the maintenance of CD8(+) T cell function and control of persistent viral infections. To investigate the potential role of IL-21 in a chronic human viral infection, we studied the rare subset of HIV-1 controllers, who are able to spontaneously control HIV-1 replication without treatment. HIV-specific triggering of IL-21 by CD4(+) T cells was significantly enriched in these persons (P = 0.0007), while isolated loss of IL-21-secreting CD4(+) T cells was characteristic for subjects with persistent viremia and progressive disease. IL-21 responses were mediated by recognition of discrete epitopes largely in the Gag protein, and expansion of IL-21(+) CD4(+) T cells in acute infection resulted in lower viral set points (P = 0.002). Moreover, IL-21 production by CD4(+) T cells of HIV controllers enhanced perforin production by HIV-1-specific CD8(+) T cells from chronic progressors even in late stages of disease, and HIV-1-specific effector CD8(+) T cells showed an enhanced ability to efficiently inhibit viral replication in vitro after IL-21 binding. These data suggest that HIV-1-specific IL-21(+) CD4(+) T cell responses might contribute to the control of viral replication in humans and are likely to be of great importance for vaccine design.
journal_name
J Viroljournal_title
Journal of virologyauthors
Chevalier MF,Jülg B,Pyo A,Flanders M,Ranasinghe S,Soghoian DZ,Kwon DS,Rychert J,Lian J,Muller MI,Cutler S,McAndrew E,Jessen H,Pereyra F,Rosenberg ES,Altfeld M,Walker BD,Streeck Hdoi
10.1128/JVI.02030-10subject
Has Abstractpub_date
2011-01-01 00:00:00pages
733-41issue
2eissn
0022-538Xissn
1098-5514pii
JVI.02030-10journal_volume
85pub_type
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