IL-2 limits IL-12 enhanced lymphocyte proliferation during Leishmania amazonensis infection

Amanda Ramer-Tait, Christine A. Petersen, Douglas E. Jones

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44hiCD4+ T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44hiCD4+ T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4+ T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional Treg cells.

Original languageEnglish (US)
Pages (from-to)32-39
Number of pages8
JournalCellular Immunology
Volume270
Issue number1
DOIs
StatePublished - Jul 6 2011

Fingerprint

Leishmania
Interleukin-12
Interleukin-2
Lymphocytes
Infection
T-Lymphocytes
Antigens
Parasite Load
Inbred C3H Mouse
Regulatory T-Lymphocytes
Immunosuppressive Agents
Cell Proliferation
Cytokines
Phenotype
Antibodies

Keywords

  • IL-12
  • IL-2
  • Leishmania
  • T cell
  • Tolerance

ASJC Scopus subject areas

  • Immunology

Cite this

IL-2 limits IL-12 enhanced lymphocyte proliferation during Leishmania amazonensis infection. / Ramer-Tait, Amanda; Petersen, Christine A.; Jones, Douglas E.

In: Cellular Immunology, Vol. 270, No. 1, 06.07.2011, p. 32-39.

Research output: Contribution to journalArticle

Ramer-Tait, Amanda ; Petersen, Christine A. ; Jones, Douglas E. / IL-2 limits IL-12 enhanced lymphocyte proliferation during Leishmania amazonensis infection. In: Cellular Immunology. 2011 ; Vol. 270, No. 1. pp. 32-39.
@article{263d474633a442628e299168a3143c37,
title = "IL-2 limits IL-12 enhanced lymphocyte proliferation during Leishmania amazonensis infection",
abstract = "C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44hiCD4+ T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44hiCD4+ T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4+ T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional Treg cells.",
keywords = "IL-12, IL-2, Leishmania, T cell, Tolerance",
author = "Amanda Ramer-Tait and Petersen, {Christine A.} and Jones, {Douglas E.}",
year = "2011",
month = "7",
day = "6",
doi = "10.1016/j.cellimm.2011.03.016",
language = "English (US)",
volume = "270",
pages = "32--39",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - IL-2 limits IL-12 enhanced lymphocyte proliferation during Leishmania amazonensis infection

AU - Ramer-Tait, Amanda

AU - Petersen, Christine A.

AU - Jones, Douglas E.

PY - 2011/7/6

Y1 - 2011/7/6

N2 - C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44hiCD4+ T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44hiCD4+ T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4+ T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional Treg cells.

AB - C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44hiCD4+ T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44hiCD4+ T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4+ T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional Treg cells.

KW - IL-12

KW - IL-2

KW - Leishmania

KW - T cell

KW - Tolerance

UR - http://www.scopus.com/inward/record.url?scp=79959839795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959839795&partnerID=8YFLogxK

U2 - 10.1016/j.cellimm.2011.03.016

DO - 10.1016/j.cellimm.2011.03.016

M3 - Article

VL - 270

SP - 32

EP - 39

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 1

ER -