Allergy Asthma Immunol Res.  2018 Jan;10(1):77-82. 10.4168/aair.2018.10.1.77.

T-Helper Type 2 Cells Direct Antigen-Induced Eosinophilic Skin Inflammation in Mice

• Kaminuma O
• Nishimura
• Kitamura N
• Saeki M
• Hiroi T
• Mori A

• KMID: 2428852
• DOI: http://doi.org/10.4168/aair.2018.10.1.77

Abstract

Eosinophilic inflammation in combination with immunoglobulin E (IgE) production is a characteristic feature of atopic dermatitis. Although activated T-helper type (Th) 2 cells play critical roles in the local accumulation and activation of eosinophils, whether they induce eosinophilic skin inflammation, independent of the IgE-mediated pathway has been unclear. To address the functional role of T cells in allergic skin diseases, we herein transferred Th1/Th2-differentiated or naive DO11.10 T cells into unprimed BALB/c mice. Ovalbumin-specific Th2 cells, as well as eosinophils, accumulated in the skin upon antigen challenge, despite the absence of antigen-specific IgE. Neither antigen-specific Th1 nor naive T cells induced eosinophil accumulation, although Th1 cells by themselves migrated into the skin. Interleukin (IL)-4, IL-5, and eotaxin were specifically produced in the skin of antigen-challenged, Th2 cell-transferred mice, whereas interferon (IFN)-γ and regulated on activation, normal T cell expressed and secreted (RANTES) were preferentially produced in Th1 cells-transferred mice. Production of monocyte chemoattractant protein (MCP)-1 and MCP-3 was enhanced by both Th1 and Th2 cells. The accumulation of eosinophils and Th2 cells in the skin was suppressed by both dexamethasone and FK506, indicating an essential role of Th2 cells in eosinophil recruitment. We conclude that Th2 cells can induce eosinophilic infiltration into the skin in the absence of antigen-specific IgE.

Keyword

Atopic dermatitis; chemokines; cytokines; eosinophils; immunoglobulin E; T-lymphocytes

MeSH Terms

Animals
Chemokines
Cytokines
Dermatitis, Atopic
Dexamethasone
Eosinophils*
Immunoglobulin E
Immunoglobulins
Inflammation*
Interferons
Interleukin-5
Interleukins
Mice*
Monocytes
Skin Diseases
Skin*
T-Lymphocytes
Tacrolimus
Th1 Cells
Th2 Cells
Chemokines
Cytokines
Dexamethasone
Immunoglobulin E
Immunoglobulins
Interferons
Interleukin-5
Interleukins
Tacrolimus

Figure

• 

  Fig. 1 induced migration of T cells and eosinophils in the skin tissues of OVA-reactive T cell-transferred mice. Naive or Th1/Th2-differentiated DO11.10 T cells (3×107) were stained with CFSE and transferred to wildtype mice by intravenous injection. After 24 hours, these mice were challenged with 300 µg/mL OVA or BSA. Twenty-four hours after challenge, the CFSE-positive, antigen-specific T cells and eosinophils in SCF and EPO activity in the skin tissues were measured (A). Data are expressed as the mean±SEM (n=5-6). Four days after challenge, a skin specimen was taken, stained with hematoxylin-eosin, and observed under optical microscopy (B). The low and high magnification images shown in the upper and lower panels, respectively, are representative of three-four animals. Representative eosinophils are indicated by arrow heads. Bar=50 µm. OVA, ovalbumin; Th, T-helper type; CFSE, 5 (and 6)-carboxyfluorescein diacetate succinimidyl ester; BSA, bovine serum albumin; SCF, skin-chamber fluid; EPO, eosinophil peroxidase; SEM, standard error of mean. *P<0.05; †P<0.01 (Student's t test).

• 

  Fig. 2 Effects of Dex and FK on antigen-induced Th2 cell migration and upregulation of EPO activity in the skin. Th2 cells (3×107) were transferred to wildtype mice by intravenous injection. After 24 hours, these mice were challenged with 300 µg/mL OVA or BSA. Indicated doses of Dex and FK were administered subcutaneously 30 minutes before challenge. Twenty-four hours after challenge, the number of CFSE-positive cells in the SCF and EPO activity in the skin tissues were measured. Data are expressed as the mean±SEM (n=5-6). Dex, dexamethasone; FK, FK506; Th, T-helper type; EPO, eosinophil peroxidase; OVA, ovalbumin; BSA, bovine serum albumin; CFSE, carboxyfluorescein diacetate succinimidyl ester; SCF, skin-chamber fluid; SEM, standard error of mean. *P<0.05 (Bonferroni's method).

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