Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-γ

Richard E Goodman, Frank Nestle, Yathi M. Naidu, Jonathan M. Green, Craig B. Thompson, Brian J. Nickoloff, Laurence A. Turka

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

By using superantigens, we have found previously that keratinocytes activated by IFN-γ could serve as accessory cells, providing costimulatory signals needed to induce T cell proliferation. Here, we compared the profile of cytokines produced by T cells stimulated in the presence of activated keratinocytes with the response seen using professional APCs. When keratinocytes are used as accessory cells there is a specific defect in T cell IFN-γ production, whereas IL-2 and IL-4 are induced at levels comparable with those seen when professional APCs are used as accessory cells. Because keratinocytes express BB-1, a CD28-ligand distinct from B7-1 or B7-2 (which are found on professional APCs), we examined the possibility that the defect in IFN-γ production might be a result of nonproductive CD28 engagement. However, even when the CD28 pathway is directly activated by a stimulatory mAb, there is no induction of IFN-γ production in keratinocyte- supported cultures. In these same cultures IL-2 production is increased 10- fold, thus demonstrating a specific deficiency in the induction of IFN-γ rather than a failure to respond to CD28 stimulation. Analysis by reverse transcriptase-PCR and ELISA for the inducible p40 chain of IL-12 reveals that keratinocytes produce little if any messenger RNA and no protein for IL-12 p40 compared with professional APCs. Addition of rIL-12 to keratinocyte- supported cultures restores IFN-γ levels to those seen when professional APCs are present. Finally, when T cells are restimulated and analyzed at later time points (10 to 14 days) we find a refinement in cytokine profiles: T cells stimulated in the presence of professional APCs produced the Th1 cytokines IL-2 and IFN-γ, whereas T cells stimulated in the presence of activated keratinocytes produced only the Th2 cytokine IL-4. The specific ability of keratinocytes to induce a Th2 response seems most closely linked to their absence of IL-12 production, and may be important in the maintenance of peripheral tolerance to self-Ags or in the immune response to exogenous Ags, pathogens, or haptens encountered in skin.

Original languageEnglish (US)
Pages (from-to)5189-5198
Number of pages10
JournalJournal of Immunology
Volume152
Issue number11
StatePublished - Jun 1 1994

Fingerprint

Keratinocytes
Interleukin-4
Interleukin-2
T-Lymphocytes
Interleukin-12
Cytokines
CD80 Antigens
Peripheral Tolerance
Superantigens
Haptens
Reverse Transcriptase Polymerase Chain Reaction
Enzyme-Linked Immunosorbent Assay
Maintenance
Cell Proliferation
Messenger RNA
Skin

ASJC Scopus subject areas

  • Immunology

Cite this

Goodman, R. E., Nestle, F., Naidu, Y. M., Green, J. M., Thompson, C. B., Nickoloff, B. J., & Turka, L. A. (1994). Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-γ. Journal of Immunology, 152(11), 5189-5198.

Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-γ. / Goodman, Richard E; Nestle, Frank; Naidu, Yathi M.; Green, Jonathan M.; Thompson, Craig B.; Nickoloff, Brian J.; Turka, Laurence A.

In: Journal of Immunology, Vol. 152, No. 11, 01.06.1994, p. 5189-5198.

Research output: Contribution to journalArticle

Goodman, RE, Nestle, F, Naidu, YM, Green, JM, Thompson, CB, Nickoloff, BJ & Turka, LA 1994, 'Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-γ', Journal of Immunology, vol. 152, no. 11, pp. 5189-5198.
Goodman RE, Nestle F, Naidu YM, Green JM, Thompson CB, Nickoloff BJ et al. Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-γ. Journal of Immunology. 1994 Jun 1;152(11):5189-5198.
Goodman, Richard E ; Nestle, Frank ; Naidu, Yathi M. ; Green, Jonathan M. ; Thompson, Craig B. ; Nickoloff, Brian J. ; Turka, Laurence A. / Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-γ. In: Journal of Immunology. 1994 ; Vol. 152, No. 11. pp. 5189-5198.
@article{478a3852ccaa471bacc7f3b23f7d791a,
title = "Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-γ",
abstract = "By using superantigens, we have found previously that keratinocytes activated by IFN-γ could serve as accessory cells, providing costimulatory signals needed to induce T cell proliferation. Here, we compared the profile of cytokines produced by T cells stimulated in the presence of activated keratinocytes with the response seen using professional APCs. When keratinocytes are used as accessory cells there is a specific defect in T cell IFN-γ production, whereas IL-2 and IL-4 are induced at levels comparable with those seen when professional APCs are used as accessory cells. Because keratinocytes express BB-1, a CD28-ligand distinct from B7-1 or B7-2 (which are found on professional APCs), we examined the possibility that the defect in IFN-γ production might be a result of nonproductive CD28 engagement. However, even when the CD28 pathway is directly activated by a stimulatory mAb, there is no induction of IFN-γ production in keratinocyte- supported cultures. In these same cultures IL-2 production is increased 10- fold, thus demonstrating a specific deficiency in the induction of IFN-γ rather than a failure to respond to CD28 stimulation. Analysis by reverse transcriptase-PCR and ELISA for the inducible p40 chain of IL-12 reveals that keratinocytes produce little if any messenger RNA and no protein for IL-12 p40 compared with professional APCs. Addition of rIL-12 to keratinocyte- supported cultures restores IFN-γ levels to those seen when professional APCs are present. Finally, when T cells are restimulated and analyzed at later time points (10 to 14 days) we find a refinement in cytokine profiles: T cells stimulated in the presence of professional APCs produced the Th1 cytokines IL-2 and IFN-γ, whereas T cells stimulated in the presence of activated keratinocytes produced only the Th2 cytokine IL-4. The specific ability of keratinocytes to induce a Th2 response seems most closely linked to their absence of IL-12 production, and may be important in the maintenance of peripheral tolerance to self-Ags or in the immune response to exogenous Ags, pathogens, or haptens encountered in skin.",
author = "Goodman, {Richard E} and Frank Nestle and Naidu, {Yathi M.} and Green, {Jonathan M.} and Thompson, {Craig B.} and Nickoloff, {Brian J.} and Turka, {Laurence A.}",
year = "1994",
month = "6",
day = "1",
language = "English (US)",
volume = "152",
pages = "5189--5198",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-γ

AU - Goodman, Richard E

AU - Nestle, Frank

AU - Naidu, Yathi M.

AU - Green, Jonathan M.

AU - Thompson, Craig B.

AU - Nickoloff, Brian J.

AU - Turka, Laurence A.

PY - 1994/6/1

Y1 - 1994/6/1

N2 - By using superantigens, we have found previously that keratinocytes activated by IFN-γ could serve as accessory cells, providing costimulatory signals needed to induce T cell proliferation. Here, we compared the profile of cytokines produced by T cells stimulated in the presence of activated keratinocytes with the response seen using professional APCs. When keratinocytes are used as accessory cells there is a specific defect in T cell IFN-γ production, whereas IL-2 and IL-4 are induced at levels comparable with those seen when professional APCs are used as accessory cells. Because keratinocytes express BB-1, a CD28-ligand distinct from B7-1 or B7-2 (which are found on professional APCs), we examined the possibility that the defect in IFN-γ production might be a result of nonproductive CD28 engagement. However, even when the CD28 pathway is directly activated by a stimulatory mAb, there is no induction of IFN-γ production in keratinocyte- supported cultures. In these same cultures IL-2 production is increased 10- fold, thus demonstrating a specific deficiency in the induction of IFN-γ rather than a failure to respond to CD28 stimulation. Analysis by reverse transcriptase-PCR and ELISA for the inducible p40 chain of IL-12 reveals that keratinocytes produce little if any messenger RNA and no protein for IL-12 p40 compared with professional APCs. Addition of rIL-12 to keratinocyte- supported cultures restores IFN-γ levels to those seen when professional APCs are present. Finally, when T cells are restimulated and analyzed at later time points (10 to 14 days) we find a refinement in cytokine profiles: T cells stimulated in the presence of professional APCs produced the Th1 cytokines IL-2 and IFN-γ, whereas T cells stimulated in the presence of activated keratinocytes produced only the Th2 cytokine IL-4. The specific ability of keratinocytes to induce a Th2 response seems most closely linked to their absence of IL-12 production, and may be important in the maintenance of peripheral tolerance to self-Ags or in the immune response to exogenous Ags, pathogens, or haptens encountered in skin.

AB - By using superantigens, we have found previously that keratinocytes activated by IFN-γ could serve as accessory cells, providing costimulatory signals needed to induce T cell proliferation. Here, we compared the profile of cytokines produced by T cells stimulated in the presence of activated keratinocytes with the response seen using professional APCs. When keratinocytes are used as accessory cells there is a specific defect in T cell IFN-γ production, whereas IL-2 and IL-4 are induced at levels comparable with those seen when professional APCs are used as accessory cells. Because keratinocytes express BB-1, a CD28-ligand distinct from B7-1 or B7-2 (which are found on professional APCs), we examined the possibility that the defect in IFN-γ production might be a result of nonproductive CD28 engagement. However, even when the CD28 pathway is directly activated by a stimulatory mAb, there is no induction of IFN-γ production in keratinocyte- supported cultures. In these same cultures IL-2 production is increased 10- fold, thus demonstrating a specific deficiency in the induction of IFN-γ rather than a failure to respond to CD28 stimulation. Analysis by reverse transcriptase-PCR and ELISA for the inducible p40 chain of IL-12 reveals that keratinocytes produce little if any messenger RNA and no protein for IL-12 p40 compared with professional APCs. Addition of rIL-12 to keratinocyte- supported cultures restores IFN-γ levels to those seen when professional APCs are present. Finally, when T cells are restimulated and analyzed at later time points (10 to 14 days) we find a refinement in cytokine profiles: T cells stimulated in the presence of professional APCs produced the Th1 cytokines IL-2 and IFN-γ, whereas T cells stimulated in the presence of activated keratinocytes produced only the Th2 cytokine IL-4. The specific ability of keratinocytes to induce a Th2 response seems most closely linked to their absence of IL-12 production, and may be important in the maintenance of peripheral tolerance to self-Ags or in the immune response to exogenous Ags, pathogens, or haptens encountered in skin.

UR - http://www.scopus.com/inward/record.url?scp=0028233727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028233727&partnerID=8YFLogxK

M3 - Article

VL - 152

SP - 5189

EP - 5198

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -