Natural Killer Cell Functions and Subsets After In Vitro Stimulation with IL-2 and IL-12, with Special Emphasis on Intracellular IFN-γ and NK-Cell Cytotoxicity |
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Authors: | R Nyboe T Rix J Krog E Tønnesen & M Hokland |
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Institution: | Department of Immunology, Landspitali University Hospital, Reykjavik, Iceland. E-mail: heklas@landspitali.is |
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Abstract: | The interaction with adhesion molecules expressed by vascular endothelium is the first step in lymphocyte infiltration into tissues. At both cutaneous and mucosal sites interleukin-10 (IL-10), IL-12 and transforming growth factor (TGF)-β are important regulators of chronic inflammatory disease, where cutaneous lymphocyte-associated antigen (CLA) and αE integrin (CD103) may be expressed. Unlike CLA, CD103 is not believed to play a role in tissue-specific homing but may help to retain T cells within epithelial layers. We have previously shown that IL-12 alone can together with an unknown cofactor increase the expression of CLA. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8+ but not CD4+ T cells. While IL-12 increased superantigen-stimulated expression of CLA, this cytokine strongly inhibited the CD103 expression, and a combination of IL-12 and TGF-β completely abrogated the induced CD103 expression. Conversely, IL-10 suppressed CLA but increased CD103 expression. These findings indicate that, in addition to suppressing the development of Th1-mediated inflammatory responses, IL-10 may also inhibit the migration of CD8+ T cells into the skin while IL-12 promotes such migration. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL-10 and IL-12, and the balance between these cytokines could influence the T-cell migration of inflammatory cells into epithelial tissues. |
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