TY - JOUR
T1 - Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection
AU - Estes, Jacob D.
AU - Li, Qingsheng
AU - Reynolds, Matthew R.
AU - Wietgrefe, Stephen
AU - Duan, Lijie
AU - Schacker, Timothy
AU - Picker, Louis J.
AU - Watkins, David I.
AU - Lifson, Jeffrey D.
AU - Reilly, Cavan
AU - Carlis, John
AU - Haase, Ashley T.
N1 - Funding Information:
Financial support: National Institutes of Health (grants R01 AI48484 and AI056997 to A.T.H.; grant T32 AI07421 to J.D.E.; grant U51 RR00169 to the California National Primate Research Center; grants R01 AI51239 and R01 AI51596 to C.J.M.; and grant P51 RR00167 to the Wisconsin National Primate Research Center); National Cancer Institute (contract NO1-CO-124000 to J.D.L.).
PY - 2006/3/1
Y1 - 2006/3/1
N2 - Here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent human immunodeficiency virus infection is an early regulatory T (Treg) cell response that blunts virus-specific responses. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model, we show that, indeed, viral replication and immune activation in lymphatic tissue drive a premature immunosuppressive response, with dramatic increases in the frequencies of CD4+CD25+FOXP3+ Treg cells, transforming growth factor-β1+ cells, interleukin-10+ cells, and indoleamine 2,3-dioxygenase+CD3+ cells. When we compared SIV infection with rhesus cytomegalovirus (RhCMV) infection, we found that the frequency of Treg cells paralleled the magnitude of immune activation during both infections but that the magnitude of immune activation and of the Treg cell response were lower and peaked much later during RhCMV infection. Importantly, the frequency of Treg cells inversely correlated with the magnitude of the SIV-specific cytotoxic T lymphocyte response. We conclude that an early Treg cell response during acute SIV infection may contribute to viral persistence by prematurely limiting the antiviral immune response before infection is cleared.
AB - Here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent human immunodeficiency virus infection is an early regulatory T (Treg) cell response that blunts virus-specific responses. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model, we show that, indeed, viral replication and immune activation in lymphatic tissue drive a premature immunosuppressive response, with dramatic increases in the frequencies of CD4+CD25+FOXP3+ Treg cells, transforming growth factor-β1+ cells, interleukin-10+ cells, and indoleamine 2,3-dioxygenase+CD3+ cells. When we compared SIV infection with rhesus cytomegalovirus (RhCMV) infection, we found that the frequency of Treg cells paralleled the magnitude of immune activation during both infections but that the magnitude of immune activation and of the Treg cell response were lower and peaked much later during RhCMV infection. Importantly, the frequency of Treg cells inversely correlated with the magnitude of the SIV-specific cytotoxic T lymphocyte response. We conclude that an early Treg cell response during acute SIV infection may contribute to viral persistence by prematurely limiting the antiviral immune response before infection is cleared.
UR - http://www.scopus.com/inward/record.url?scp=33144476838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33144476838&partnerID=8YFLogxK
U2 - 10.1086/500368
DO - 10.1086/500368
M3 - Article
C2 - 16453267
AN - SCOPUS:33144476838
SN - 0022-1899
VL - 193
SP - 703
EP - 712
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -