Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection.
The precise immunological role played by CD4(+) T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental CD8(+) cell depletion, elite controlling macaques with set-point viral loads < or = 500 viral RNA copies/mL mounted robust Gag- and Nef-specific CD4(+) T cell responses during reestablishment of control with > or = 54% of all virus-specific CD4(+) T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific CD4(+) T cells neither recognized nor suppressed viral replication in SIV-infected CD4(+) T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific CD4(+) T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific CD4(+) T cells may contribute directly to elite control by inhibiting viral replication in macrophages.
Sacha
Jonah B
JB
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715, USA. jbsacha@wisc.edu
Giraldo-Vela
Juan P
JP
Buechler
Matthew B
MB
Martins
Mauricio A
MA
Maness
Nicholas J
NJ
Chung
Chungwon
C
Wallace
Lyle T
LT
León
Enrique J
EJ
Friedrich
Thomas C
TC
Wilson
Nancy A
NA
Hiraoka
Atsunobu
A
Watkins
David I
DI
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism*; D015693:Gene Products, nef / Q000378:metabolism*; D008253:Macaca mulatta; D008264:Macrophages / Q000821:virology*; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology*
D015683:Gene Products, gag; D015693:Gene Products, nef; D012367:RNA, Viral