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.
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.


CONCLUSIONS
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.
Woodward
A L
AL
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
Spergel
J M
JM
Alenius
H
H
Mizoguchi
E
E
Bhan
A K
AK
Castigli
E
E
Brodeur
S R
SR
Oettgen
H C
HC
Geha
R S
RS
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000378:metabolism*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D007114:Immunization; D015847:Interleukin-4 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D012867:Skin / Q000276:immunology / Q000378:metabolism
D019013:CD40 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023201:CD40 Ligand; D015847:Interleukin-4; D010047:Ovalbumin