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Activated Human Neonatal CD8⁺ T Cells Are Subject to Immunomodulation by Direct TLR2 or TLR5 Stimulation¹

Mark McCarron^2,*, and Denis J. Reen^*,

^* Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland; and University College Dublin Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland

In conditions of optimal priming, the neonate possess competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonates’ natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8⁺ T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam₃Cys (palmitoyl-3-Cys-Ser-(Lys)₄) and flagellin monomers significantly enhanced proliferation, CD25⁺ expression, IL-2, IFN-, TNF-, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8⁺ T cells. Blocking studies confirmed that the increase in IFN- production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8⁺ T cells to both TLR agonists had an additive effect on IFN- production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8⁺ component.

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 a grant from the Children’s Medical and Research Foundation (RP350) (to M.M.).

² Address correspondence and reprint requests to Dr. Mark McCarron, Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland. E-mail address: mark.mccarron{at}ucd.ie

³ Abbreviations used in this paper: Pam₃Cys, palmitoyl-3-Cys-Ser-(Lys)₄; FSL-1, fibroblast-stimulating lipopeptide-1.

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