Coordination of early protective immunity to viral infection by regulatory T cells.
Suppression of immune responses by regulatory T cells (Tregs) is thought to limit late stages of pathogen-specific immunity as a means of minimizing associated tissue damage. We examined a role for Tregs during mucosal herpes simplex virus infection in mice, and observed an accelerated fatal infection with increased viral loads in the mucosa and central nervous system after ablation of Tregs. Although augmented interferon production was detected in the draining lymph nodes (dLNs) in Treg-deprived mice, it was profoundly reduced at the infection site. This was associated with a delay in the arrival of natural killer cells, dendritic cells, and T cells to the site of infection and a sharp increase in proinflammatory chemokine levels in the dLNs. Our results suggest that Tregs facilitate early protective responses to local viral infection by allowing a timely entry of immune cells into infected tissue.
Lund
Jennifer M
JM
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Hsing
Lianne
L
Pham
Thuy T
TT
Rudensky
Alexander Y
AY
D000818:Animals; D002634:Chemotaxis, Leukocyte; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D006558:Herpes Genitalis / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007109:Immunity; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016898:Interferon-alpha; D007371:Interferon-gamma