Expansion and exhaustion of T-cell responses during mutational escape from long-term viral control in two DNA/modified vaccinia virus Ankara-vaccinated and simian-human immunodeficiency virus SHIV-89.6P-challenged macaques.
In this study, we monitored the temporal breadths, frequencies, and functions of antiviral CD4 and CD8 T cells in 2 of 22 DNA/modified vaccinia virus Ankara-vaccinated macaques that lost control of a simian-human immunodeficiency virus 89.6P challenge by 196 weeks postchallenge. Our results show that both mutation and exhaustion contributed to escape. With the reappearance of viremia, responding CD8 and CD4 T cells underwent an initial increase and then loss of breadth and frequency. Antiviral gamma interferon (IFN-gamma)- and interleukin 2-coproducing cells were lost before IFN-gamma-producing cells and CD4 cells before CD8 cells. At euthanasia, all CD8, but no CD4, Gag epitopes detected during long-term control contained mutations.
Sadagopal
Shanmugalakshmi
S
Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.
Amara
Rama Rao
RR
Kannanganat
Sunil
S
Sharma
Sunita
S
Chennareddi
Lakshmi
L
Robinson
Harriet L
HL
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000235:genetics; D006678:HIV / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008251:Macaca; D009154:Mutation / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D014765:Viral Vaccines / Q000276:immunology; D014766:Viremia
D000939:Epitopes; D007376:Interleukin-2; D012367:RNA, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma