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T Regulatory Cells Contribute to the Attenuated Primary CD8+ and CD4+ T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice
Marian A. Fernandez, Franz K. Puttur, Yuan M. Wang, Wade Howden, Stephen I. Alexander and Cheryl A. Jones
J Immunol February 1, 2008, 180 (3) 1556-1564; DOI: https://doi.org/10.4049/jimmunol.180.3.1556
Marian A. Fernandez
Centre for Perinatal Infection Research,
Franz K. Puttur
Centre for Perinatal Infection Research, Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
Yuan M. Wang
Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia, and
Wade Howden
Stephen I. Alexander
Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, AustraliaCentre for Kidney Research, The Children's Hospital at Westmead, Westmead, New South Wales, Australia, and
Cheryl A. Jones
The first weeks of life are characterized by immune tolerance and increased susceptibility to intracellular pathogens. The neonatal adaptive response to HSV is attenuated compared with adult control models in humans and mice. T Regulatory cells (Tregs) control autoimmunity and excessive immune responses to infection. We therefore compared Treg responses in the draining lymph nodes (LN) of HSV-infected neonatal and adult C57BL/6 mice with the effect of Treg depletion/inactivation by anti-CD25 (PC61) treatment before infection on Ag-specific T cell effector responses at this site. There was a small, but significant increase in the frequency of CD4+Foxp3+ Tregs at day 3 postinfection (p.i.) in the LN of neonatal and adult mice, compared with age-matched mock-infected controls. Depletion of Tregs before HSV infection significantly enhanced HSV-specific CD8+ T cell cytotoxicity in vivo, cell number, activation, and granzyme B expression 4 days p.i. only in neonatal mice, and significantly enhanced CD8+ and CD4+ T cell IFN-γ responses in both infected adults and neonates. Treg depletion also reduced the titer of infectious virus in the draining LN and nervous system of infected neonates on days 2 and 3 p.i. Treg suppression of the neonatal CTL response p.i. with HSV was associated with increased expression of TGF-β in the draining LN at day 4 p.i. compared with uninfected neonates, but IL-10 was increased in infected adults alone. These experiments support the notion that the newborn primary T cell effector responses to HSV are suppressed by Tregs.
Received November 16, 2007.
Accepted November 16, 2007.
Copyright © 2008 by The American Association of Immunologists
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Marian A. Fernandez, Franz K. Puttur, Yuan M. Wang, Wade Howden, Stephen I. Alexander, Cheryl A. Jones
The Journal of Immunology February 1, 2008, 180 (3) 1556-1564; DOI: 10.4049/jimmunol.180.3.1556
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