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,
* Centre for Perinatal Infection Research,
Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia, and
Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
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-
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by The Children’s Hospital at Westmead Research Scholar Award (to C.A.J.).
2 Address correspondence and reprint requests to Dr. Cheryl A. Jones, Centre for Perinatal Infection Research, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia. E-mail address: cherylj{at}chw.edu.au
3 Abbreviations used in this paper: Treg, T regulatory cell; p.i., postinfection; wt, wild type; LN, lymph node.
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