Proteolytic cleavage of CD25, the alpha subunit of the human T cell interleukin 2 receptor, by Der p 1, a major mite allergen with cysteine protease activity

Abstract

Recent reports have indicated that the cysteine protease activity of Der p 1 may play a significant role in its ability to elicit IgE antibody responses, mainly through cleavage of membrane CD23 on B cells and interleukin (IL)-4 synthesis and secretion from mast cells and basophils. Here we demonstrate for the first time that Der p 1 also cleaves the alpha subunit of the IL-2 receptor (IL-2R or CD25) from the surface of human peripheral blood T cells and, as a result, these cells show markedly diminished proliferation and interferon gamma secretion in response to potent stimulation by anti-CD3 antibody. Given that the IL-2R is pivotal for the propagation of Th1 cells, its cleavage by Der p 1 may consequently bias the immune response towards Th2 cells, thereby creating an allergic microenvironment.

Figure 1

The proteolytic effect of Der p 1 on human T cell surface markers. Paired results represent the expression of markers in the absence (open bars) and presence (solid bars) of Der p 1 (5 μg/ml). Data presented are the means of duplicate experiments; SE was <5%.

Figure 2

(a) Der p 1–induced cleavage of membrane CD25 (filled circles) and concomitant release of soluble CD25 (open circles). (b) CD25 cleavage is blocked by earlier treatment of Der p 1 (5 μg/ml) with antipain (4 μM). Data presented in a and b are the means of duplicate experiments; SE was <5%.

Figure 2

(a) Der p 1–induced cleavage of membrane CD25 (filled circles) and concomitant release of soluble CD25 (open circles). (b) CD25 cleavage is blocked by earlier treatment of Der p 1 (5 μg/ml) with antipain (4 μM). Data presented in a and b are the means of duplicate experiments; SE was <5%.

Figure 3

Der p 1 suppresses human T cell proliferation mostly within 18–48 h of culture initiation. Results represent cultures with no Der p 1 (open bar) or those to which Der p 1 (10 μg/ml) was added at different time points (solid bars). The thymidine label was added 80 h after culture initiation. Data presented are the means of quadruplicate experiments; error bars represent SEM.

Figure 4

Effect of Der p 1 (10 μg/ml; added 6 h after culture initiation) on the time course of Th1 cytokine expression and soluble CD25 release. Data represent the kinetics of IL-2 expression (a) soluble CD25 release (b), and IFN-γ expression (c) in the absence (open circles) and presence (filled circles) of Der p 1. Data presented are the means of duplicate experiments; SE was <5%.

Figure 4

Effect of Der p 1 (10 μg/ml; added 6 h after culture initiation) on the time course of Th1 cytokine expression and soluble CD25 release. Data represent the kinetics of IL-2 expression (a) soluble CD25 release (b), and IFN-γ expression (c) in the absence (open circles) and presence (filled circles) of Der p 1. Data presented are the means of duplicate experiments; SE was <5%.

Figure 4

Effect of Der p 1 (10 μg/ml; added 6 h after culture initiation) on the time course of Th1 cytokine expression and soluble CD25 release. Data represent the kinetics of IL-2 expression (a) soluble CD25 release (b), and IFN-γ expression (c) in the absence (open circles) and presence (filled circles) of Der p 1. Data presented are the means of duplicate experiments; SE was <5%.