Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells

Sigmundsdóttir, H.; Johnston, A.; Gudjónsson, J. E.; Valdimarsson, H.

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.