Fel d 1-derived T cell peptide therapy induces recruitment of CD4+ CD25+; CD4+ interferon-gamma+ T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects.
BACKGROUND
Specific immunotherapy with whole allergen extracts is associated with local accumulation of IFN-gamma+ and CD25+ cells indicating recruitment of activated T-helper type 1 (Th1) and/or T regulatory cells. We have studied allergen-induced, late-phase skin biopsies before and after T cell peptide therapy for evidence of alterations in the pattern of local recruitment of Th1, T-helper type 2 (Th2) and T regulatory cells.


OBJECTIVE
To evaluate the effect of T cell peptide therapy on the allergen-induced cutaneous late-phase reaction.


METHODS
Increasing doses of synthetic Fel d 1-derived peptides were administered (by intradermal injection) to eight cat-allergic asthmatics at 14-day intervals. Twenty-four-hour skin biopsies were taken from whole cat allergen- and diluent-injected sites, before and after treatment and studied by immunohistochemistry and in situ hybridization.


RESULTS
Fel-d 1 peptides decreased airway hyper-responsiveness (P = 0.02) and inhibited the late-phase cutaneous reaction (LPCR) to whole cat allergen (P = 0.03). This was associated with significant increases (post- vs. pre-treatment) in the number of cutaneous CD4+/IFN-gamma+ (P = 0.03) and CD4+/CD25+ cells (P = 0.04), but not in CD4+/IL-10+ or CD4+/CTLA-4+ cells.


CONCLUSIONS
Treatment with allergen-derived T cell peptides results in allergen-dependent recruitment to the skin of Th1, rather than T regulatory cells, to cutaneous late-phase reaction sites.
Alexander
C
C
Allergy & Clinical Immunology, Faculty of Medicine, Imperial College London, London, UK.
Ying
S
S
B Kay
A
A
Larché
M
M
D000818:Animals; D002415:Cats; D002634:Chemotaxis, Leukocyte; D003888:Desensitization, Immunologic / Q000379:methods*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D010455:Peptides / Q000008:administration & dosage*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D012867:Skin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D006023:Glycoproteins; D007378:Interleukins; D010455:Peptides; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; C059296:Fel d 1 protein, Felis domesticus