Differentiation of Resting Human Peripheral Blood γδ T Cells toward Th1- or Th2-Phenotype

doi:10.1006/cimm.2001.1850

Cellular Immunology

Volume 212, Issue 2, 15 September 2001, Pages 110-117

https://doi.org/10.1006/cimm.2001.1850 Get rights and content

Abstract

Depending on the microenvironment, murine γδ T cells differentiate into either Th1 (IFN-γ-producing) or Th2 (IL-4-producing) cells. It is unclear, however, whether circulating human peripheral blood γδ T cells can be driven into Th1 or Th2 cells by modulation of the priming cytokine milieu. In this study, peripheral blood γδ T cells were stimulated by phosphoantigen (isopentenyl pyrophosphate) or Daudi lymphoma cells in the presence of Th1-priming (rIL-12, anti-IL-4 Ab) or Th2-priming (rIL-4, anti-IL-12 Ab) conditions. Single-cell analysis of cytokine secretion (IFN-γ and IL-4) was performed by flow cytometry after 18 h and after restimulation of expanded γδ T cells. The early activation of resting γδ T cells was characterized by the induction of IFN-γ. Priming under Th1 conditions induced a Th1 profile characterized by increased secretion of IFN-γ and TNF-α, while Th2 conditions caused increased production of IL-4 (Th2 profile) by the γδ T cells. These results indicate that the major subset of human γδ T cells can be polarized into either Th1 or Th2 cytokine pattern depending on the cytokine milieu in which contact with antigen occurs.

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Citation Excerpt :
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^☆: Abbrevations used: M.tb., Mycobacterium tuberculosis; IPP, isopentenyl pyrophosphate.

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Cellular Immunology

Abstract

References (30)

The expanding universe of T-cell subsets: Th1, Th2 and more

Immunol. Today

Differential regulation of IFN-gamma, TNF-alpha, and IL-10 production by CD4(+) alphabetaTCR+ T cells and vdelta2(+) gammadelta T cells in response to monocytes infected with Mycobacterium tuberculosis-H37Ra

Cell. Immunol.

Patterns of phosphoantigen stimulation of human Vgamma9/Vdelta2 T cell clones include Th0 cytokines

Hum. Immunol.

The Th1/Th2 paradigm

Immunol. Today

Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines

J. Immunol.

Neutralizing IL-12 during induction of murine acute graft-versus-host disease polarizes the cytokine profile toward a Th2-type alloimmune response and confers long term protection from disease

J. Immunol.

Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin 12 and Pentostam

Proc. Natl. Acad. Sci. USA

TH1/TH2,3 imbalance due to cytokine-producing NK, gammadelta T and NK-gammadelta T cells in murine pregnancy decidua in success or failure of pregnancy

Am. J. Reprod. Immunol.

Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo

Nature

Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation

J. Immunol.

Dominance of IL-12 over IL-4 in gamma delta T cell differentiation leads to default production of IFN-gamma: Failure to down-regulate IL-12 receptor beta 2-chain expression

J. Immunol.

Single-cell cytokine analysis of gamma delta T cell responses to nonpeptide mycobacterial antigens

J. Immunol.

Regulation by cytokines (IL-12, IL-15, IL-4 and IL-10) of the Vgamma9Vdelta2 T cell response to mycobacterial phosphoantigens in responder and anergic HIV-infected persons

Eur. J. Immunol.

IL-15 enhances the response of human gamma delta T cells to non-peptide microbial antigens

J. Immunol.

Cited by (126)

Human gamma-delta (γδ) T cell therapy for glioblastoma: A novel alternative to overcome challenges of adoptive immune cell therapy

The way of interaction between Vγ9Vδ2 T cells and tumor cells

IL-12 conditioning of peripheral blood mononuclear cells from breast cancer patients promotes the zoledronate-induced expansion of γδ T cells in vitro and enhances their cytotoxic activity and cytokine production

Controversial role of γδ T cells in pancreatic cancer

Gamma delta (γδ) T cells in cancer immunotherapy; where it comes from, where it will go?

Cancer Immunology

Regular ArticleDifferentiation of Resting Human Peripheral Blood γδ T Cells toward Th1- or Th2-Phenotype☆

Abstract

Immunol. Today

Cell. Immunol.

Hum. Immunol.

Immunol. Today

Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines

J. Immunol.

Neutralizing IL-12 during induction of murine acute graft-versus-host disease polarizes the cytokine profile toward a Th2-type alloimmune response and confers long term protection from disease

J. Immunol.

Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin 12 and Pentostam

Proc. Natl. Acad. Sci. USA

TH1/TH2,3 imbalance due to cytokine-producing NK, gammadelta T and NK-gammadelta T cells in murine pregnancy decidua in success or failure of pregnancy

Am. J. Reprod. Immunol.

Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo

Nature

Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation

J. Immunol.

Dominance of IL-12 over IL-4 in gamma delta T cell differentiation leads to default production of IFN-gamma: Failure to down-regulate IL-12 receptor beta 2-chain expression

J. Immunol.

Single-cell cytokine analysis of gamma delta T cell responses to nonpeptide mycobacterial antigens

J. Immunol.

Regulation by cytokines (IL-12, IL-15, IL-4 and IL-10) of the Vgamma9Vdelta2 T cell response to mycobacterial phosphoantigens in responder and anergic HIV-infected persons

Eur. J. Immunol.

IL-15 enhances the response of human gamma delta T cells to non-peptide microbial antigens

J. Immunol.

Regular Article
Differentiation of Resting Human Peripheral Blood γδ T Cells toward Th1- or Th2-Phenotype☆