An obligate role for T-cell receptor alphabeta+ T cells but not T-cell receptor gammadelta+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis

J Allergy Clin Immunol. 2001 Feb;107(2):359-66. doi: 10.1067/mai.2001.112695.

Abstract

Background: We recently described a murine model of atopic dermatitis (AD) elicited by epicutaneous sensitization with ovalbumin (OVA). The skin lesions in these mice were characterized by a dermal infiltrate consisting of eosinophils and T cells and by increased expression of the TH2 cytokines IL-4 and IL-5. Epicutaneous sensitization induces a rise in the levels of serum total IgE and OVA-specific antibodies, further indicating that it elicits a predominantly TH2 response.

Objective: This study was undertaken to assess the roles of T cells, B cells, and CD40L-CD40 interactions in AD.

Methods: Mice with targeted gene deletions were sensitized with OVA. Histologic and immunohistochemical examinations, as well as measurements of IL-4 mRNA, were performed on OVA-sensitized skin. Total and antigen-specific serum IgE levels were determined.

Results: RAG2(-/-) mice, which lack both T and B cells, did not exhibit cellular infiltration, induction of dermal IL-4 mRNA, or elevation of serum IgE after OVA sensitization; all of these features were present in B-cell-deficient IgH(-/-) mice. T-cell receptor alpha(-/-) mice did not display cellular infiltration, IL-4 mRNA expression, or increased IgE levels after OVA sensitization, but these responses were elicited in T-cell receptor delta(-/-) mice after sensitization. Absence of CD40 had no effect on these responses.

Conclusion: These results suggest that alphabeta T cells, but not gammadelta T cells, B cells, or CD40L-CD40 interactions, are critical for skin inflammation and the TH2 response in AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • CD40 Antigens / physiology*
  • CD40 Ligand / physiology*
  • Dermatitis, Atopic / metabolism*
  • Disease Models, Animal
  • Eosinophils / immunology
  • Immunization
  • Interleukin-4 / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / physiology*
  • Receptors, Antigen, T-Cell, gamma-delta / physiology*
  • Skin / immunology
  • Skin / metabolism

Substances

  • CD40 Antigens
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • CD40 Ligand
  • Interleukin-4
  • Ovalbumin