The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response.
Cytotoxic CD8(+) T cells control acute viremia in many viral infections. However, most viruses that establish chronic infections evade destruction by CD8(+) T cells, and regulatory T cells (Treg) are thought to be involved in this immune evasion. We have infected transgenic mice, in which Treg can be selectively depleted, with Friend retrovirus (FV) to investigate the influence of Treg on pathogen-specific CD8(+) T-cell responses in vivo. We observed that Treg expansion during acute infection was locally defined to organs with high viral loads and massive activation of virus-specific effector CD8(+) T cells. Experimental ablation of Treg resulted in a significant increase of peak cytotoxic CD8(+) T-cell responses against FV. In addition, it prevented the development of functional exhaustion of CD8(+) T cells and significantly reduced FV loads in lymphatic organs. Surprisingly, despite the massive virus-specific CD8(+) T-cell response after temporary Treg depletion, no evidence of immunopathology was found. These results demonstrate the important role of Treg in controlling acute retrovirus-specific CD8(+) T-cell responses, and suggest that temporary manipulation of Treg might be a possible therapeutic approach in chronic infectious diseases.
Zelinskyy
Gennadiy
G
Institute for Virology, University Clinics in Essen, University of Duisburg-Essen, Essen, Germany.
Dietze
Kirsten K
KK
Hüsecken
Yvonne P
YP
Schimmer
Simone
S
Nair
Savita
S
Werner
Tanja
T
Gibbert
Kathrin
K
Kershaw
Olivia
O
Gruber
Achim D
AD
Sparwasser
Tim
T
Dittmer
Ulf
U
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D005622:Friend murine leukemia virus / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012192:Retroviridae Infections / Q000276:immunology*; D013155:Spleen Focus-Forming Viruses / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019562:Viral Load