Direct TLR-2 costimulation unmasks the proinflammatory potential of neonatal CD4+ T cells

Brian D. Sinnott, Byung Park, Mardi C. Boer, Deborah Lewinsohn, Christina Lancioni

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Neonatal CD4+ T cells have traditionally been viewed as deficient in their capacity to produce Th1 cytokines in response to polyclonal or Ag-specific stimuli. Thus, defining unique aspects of CD4+ T cell activation and development into Th1 effector cells in neonates is essential to the successful development of novel vaccines and immunotherapies to protect infants from intracellular pathogens. Using highly purified naive CD4+ T cells derived from cord and adult peripheral blood, we compared the impact of anti-CD3 stimulation plus costimulation through TLR-2 performed in the absence of APC on CD4+ T cell cytokine production, proliferation, and expression of activation markers. In both age groups, TLR-2 costimulation elicited activation of naive CD4+ T cells, characterized by robust production of IL-2 as well as key Th1-type cytokines IFN-g and TNF-a. TLR-2 costimulation also dramatically reduced naive T cell production of the immunosuppressive cytokine IL-10. We observed that neonatal naive CD4+ T cells are uniquely sensitive to TLR-2-mediated costimulation, which enabled them to produce equivalent amounts of IFN-g and more IL-2 when compared with adult responses. Thus, neonatal CD4+ T cells have a distinctive propensity to use TLR-2-mediated costimulation for development into proinflammatory Th1 effectors, and interventions that target CD4+ T cell TLR-2-mediated responses may be exploited to enhance neonatal adaptive immunity.

Original languageEnglish (US)
Pages (from-to)68-77
Number of pages10
JournalJournal of Immunology
Volume197
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

T-Lymphocytes
Cytokines
Interleukin-2
Th1 Cells
Adaptive Immunity
Immunosuppressive Agents
Interleukin-10
Immunotherapy
Vaccines
Age Groups
Newborn Infant

ASJC Scopus subject areas

  • Immunology

Cite this

Direct TLR-2 costimulation unmasks the proinflammatory potential of neonatal CD4+ T cells. / Sinnott, Brian D.; Park, Byung; Boer, Mardi C.; Lewinsohn, Deborah; Lancioni, Christina.

In: Journal of Immunology, Vol. 197, No. 1, 01.07.2016, p. 68-77.

Research output: Contribution to journalArticle

@article{2135d322d2b845b1bf30490ce2db36dd,
title = "Direct TLR-2 costimulation unmasks the proinflammatory potential of neonatal CD4+ T cells",
abstract = "Neonatal CD4+ T cells have traditionally been viewed as deficient in their capacity to produce Th1 cytokines in response to polyclonal or Ag-specific stimuli. Thus, defining unique aspects of CD4+ T cell activation and development into Th1 effector cells in neonates is essential to the successful development of novel vaccines and immunotherapies to protect infants from intracellular pathogens. Using highly purified naive CD4+ T cells derived from cord and adult peripheral blood, we compared the impact of anti-CD3 stimulation plus costimulation through TLR-2 performed in the absence of APC on CD4+ T cell cytokine production, proliferation, and expression of activation markers. In both age groups, TLR-2 costimulation elicited activation of naive CD4+ T cells, characterized by robust production of IL-2 as well as key Th1-type cytokines IFN-g and TNF-a. TLR-2 costimulation also dramatically reduced naive T cell production of the immunosuppressive cytokine IL-10. We observed that neonatal naive CD4+ T cells are uniquely sensitive to TLR-2-mediated costimulation, which enabled them to produce equivalent amounts of IFN-g and more IL-2 when compared with adult responses. Thus, neonatal CD4+ T cells have a distinctive propensity to use TLR-2-mediated costimulation for development into proinflammatory Th1 effectors, and interventions that target CD4+ T cell TLR-2-mediated responses may be exploited to enhance neonatal adaptive immunity.",
author = "Sinnott, {Brian D.} and Byung Park and Boer, {Mardi C.} and Deborah Lewinsohn and Christina Lancioni",
year = "2016",
month = "7",
day = "1",
doi = "10.4049/jimmunol.1501297",
language = "English (US)",
volume = "197",
pages = "68--77",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Direct TLR-2 costimulation unmasks the proinflammatory potential of neonatal CD4+ T cells

AU - Sinnott, Brian D.

AU - Park, Byung

AU - Boer, Mardi C.

AU - Lewinsohn, Deborah

AU - Lancioni, Christina

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Neonatal CD4+ T cells have traditionally been viewed as deficient in their capacity to produce Th1 cytokines in response to polyclonal or Ag-specific stimuli. Thus, defining unique aspects of CD4+ T cell activation and development into Th1 effector cells in neonates is essential to the successful development of novel vaccines and immunotherapies to protect infants from intracellular pathogens. Using highly purified naive CD4+ T cells derived from cord and adult peripheral blood, we compared the impact of anti-CD3 stimulation plus costimulation through TLR-2 performed in the absence of APC on CD4+ T cell cytokine production, proliferation, and expression of activation markers. In both age groups, TLR-2 costimulation elicited activation of naive CD4+ T cells, characterized by robust production of IL-2 as well as key Th1-type cytokines IFN-g and TNF-a. TLR-2 costimulation also dramatically reduced naive T cell production of the immunosuppressive cytokine IL-10. We observed that neonatal naive CD4+ T cells are uniquely sensitive to TLR-2-mediated costimulation, which enabled them to produce equivalent amounts of IFN-g and more IL-2 when compared with adult responses. Thus, neonatal CD4+ T cells have a distinctive propensity to use TLR-2-mediated costimulation for development into proinflammatory Th1 effectors, and interventions that target CD4+ T cell TLR-2-mediated responses may be exploited to enhance neonatal adaptive immunity.

AB - Neonatal CD4+ T cells have traditionally been viewed as deficient in their capacity to produce Th1 cytokines in response to polyclonal or Ag-specific stimuli. Thus, defining unique aspects of CD4+ T cell activation and development into Th1 effector cells in neonates is essential to the successful development of novel vaccines and immunotherapies to protect infants from intracellular pathogens. Using highly purified naive CD4+ T cells derived from cord and adult peripheral blood, we compared the impact of anti-CD3 stimulation plus costimulation through TLR-2 performed in the absence of APC on CD4+ T cell cytokine production, proliferation, and expression of activation markers. In both age groups, TLR-2 costimulation elicited activation of naive CD4+ T cells, characterized by robust production of IL-2 as well as key Th1-type cytokines IFN-g and TNF-a. TLR-2 costimulation also dramatically reduced naive T cell production of the immunosuppressive cytokine IL-10. We observed that neonatal naive CD4+ T cells are uniquely sensitive to TLR-2-mediated costimulation, which enabled them to produce equivalent amounts of IFN-g and more IL-2 when compared with adult responses. Thus, neonatal CD4+ T cells have a distinctive propensity to use TLR-2-mediated costimulation for development into proinflammatory Th1 effectors, and interventions that target CD4+ T cell TLR-2-mediated responses may be exploited to enhance neonatal adaptive immunity.

UR - http://www.scopus.com/inward/record.url?scp=84975295505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975295505&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1501297

DO - 10.4049/jimmunol.1501297

M3 - Article

C2 - 27194790

AN - SCOPUS:84975295505

VL - 197

SP - 68

EP - 77

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -