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Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-gamma.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1994 Jun 01; Vol. 152 (11), pp. 5189-98. - Publication Year :
- 1994
-
Abstract
- By using superantigens, we have found previously that keratinocytes activated by IFN-gamma 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-gamma 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-gamma 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-gamma 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-gamma 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-gamma 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-gamma, 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.
- Subjects :
- Antigen-Presenting Cells physiology
Base Sequence
CD28 Antigens physiology
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Humans
Interferon-gamma analysis
Interferon-gamma genetics
Interleukin-12
Interleukin-2 analysis
Interleukin-2 genetics
Interleukin-4 analysis
Interleukin-4 genetics
Interleukins physiology
Molecular Sequence Data
Polymerase Chain Reaction
RNA, Messenger analysis
Interferon-gamma biosynthesis
Interleukin-2 biosynthesis
Interleukin-4 biosynthesis
Keratinocytes physiology
T-Lymphocytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 152
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 7910619