Increased incidence of skin infections in atopy: evidence for an antigen‐specific homing defect?

Zollner, Thomas M.; Kaufmann, Roland; Platts-Mills, Thomas A.E.; Woodfolk, Judith A.

doi:10.1046/j.1365-2222.2002.01298.x

Cited by 4 publications

(2 citation statements)

References 64 publications

(63 reference statements)

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“…It seems likely that differences in Ag-specific T cell populations associated with DTH and IH are defined, not solely at the cytokine level, but at the level of TCR specificity (as previously shown), and by other T cell properties. There is evidence to suggest that expression of the skin-specific homing Ag, cutaneous lymphocyte-associated Ag, is down-regulated in T cells specific for Tri r 2 from patients with chronic dermatophytosis (38,39). Thus, differences in homing of Ag-specific T cells to anatomical sites could explain the different features of skin infection and manifestations of allergic disease associated with distinct immune responses to Trichophyton.…”

Section: Discussionmentioning

confidence: 99%

Diversity of the Human Allergen-Specific T Cell Repertoire Associated with Distinct Skin Test Reactions: Delayed-Type Hypersensitivity-Associated Major Epitopes Induce Th1- and Th2-Dominated Responses

Woodfolk

Platts-Mills

2001

The Journal of Immunology

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Distinct immune responses in humans to the Trichophyton rubrum Ag, Tri r 2, are associated with different patterns of T cell epitope recognition based on in vitro proliferation to peptides derived from this 29-kDa protein. Specifically, the amino-terminal immunodominant epitope, peptide 5 (P5), stimulates strong T cell proliferative responses in subjects with delayed (DTH), but not immediate (IH) hypersensitivity skin tests. Evidence of a role for cytokines or changes in epitope recognition over time was examined in responses to Trichophyton using primary PBMC cultures established from seven IH and seven DTH subjects. Responses stimulated by Tri r 2 were dominated by the Th1 cytokine IFN-γ (IFN-γ:IL-5 ≥ 4:1) in five DTH subjects, even in the presence of Th2-dominated responses (IFN-γ:IL-5 ≤ 3:1) to a subset of major epitopes. Paradoxically, P5 induced IL-5 and IL-10 production in DTH, but not IH subjects (p = 0.003 (IL-5), p = 0.024 (IL-10)), with no significant difference in IFN-γ levels between the two groups. In cultures from IH responders, no IL-5 was measurable after stimulation with P6 and P7 (as well as P5); this region of the molecule was shown previously to stimulate markedly reduced T cell proliferation in these individuals. Repeat proliferation assays confirmed no change in the pattern of peptide recognition after ≥20 mo in IH or DTH subjects. We conclude that T cell repertoires associated with distinct immune responses to Tri r 2 can be distinguished based on Th2 cytokine induction by DTH-associated major epitopes localizing to the amino-terminal region of the molecule.

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Section: Discussionmentioning

confidence: 99%

Diversity of the Human Allergen-Specific T Cell Repertoire Associated with Distinct Skin Test Reactions: Delayed-Type Hypersensitivity-Associated Major Epitopes Induce Th1- and Th2-Dominated Responses

Woodfolk

Platts-Mills

2001

The Journal of Immunology

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“…By contrast, tetanus toxoid-stimulated cells from the same individual elaborated Th1 cytokines and expressed higher levels of CLA (77). It was proposed that Th2 cells are less effective than Th1 cells in the immune surveillance of skin (129). Thus, ineffective recruitment of CD4 ϩ T cells into skin lesions could contribute to persistence of infection.…”

Section: Immune Mechanisms Which Govern the Allergydermatophytosis Rementioning

confidence: 99%

Allergy and Dermatophytes

Woodfolk

2005

Clin Microbiol Rev

147

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Tinea pedis (athlete's foot) and onychomycosis (infection of the toenails) caused by the dermatophyte fungus Trichophyton are highly prevalent in adults. Several Trichophyton allergens have been identified based on elicitation of immunoglobulin E antibody-mediated immediate-hypersensitivity (IH) responses. Evidence of an etiologic role for Trichophyton in asthma in some subjects with IH and chronic dermatophytosis is provided by bronchial reactivity to Trichophyton. Improvement of asthma after systemic antifungal treatment corroborates this link. A unique feature of Trichophyton allergens is the ability of the same antigen to elicit delayed-type hypersensitivity (DTH) in individuals who lack IH reactivity. Delayed responses appear to confer protection, while IH responses do not, based on the association with acute versus chronic skin infection. The amino acid sequence identity of Trichophyton allergens with diverse enzyme families supports a dual role for these proteins in fungal pathogenesis and allergic disease. Characterizing the immunologic properties of Trichophyton allergens and defining immune mechanisms which drive dichotomous responses are pivotal to understanding the dermatophyte-allergy relationship. Recent studies have identified DTH-associated major T-cell epitopes which could facilitate the development of peptide vaccines. Characterization of additional molecular targets by using new techniques may aid not only in the eradication of infection but also in the resolution of allergic symptoms

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Dermatophytosis

2011

Fundamental Medical Mycology

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Increased incidence of skin infections in atopy: evidence for an antigen‐specific homing defect?

Cited by 4 publications

References 64 publications

Diversity of the Human Allergen-Specific T Cell Repertoire Associated with Distinct Skin Test Reactions: Delayed-Type Hypersensitivity-Associated Major Epitopes Induce Th1- and Th2-Dominated Responses

Diversity of the Human Allergen-Specific T Cell Repertoire Associated with Distinct Skin Test Reactions: Delayed-Type Hypersensitivity-Associated Major Epitopes Induce Th1- and Th2-Dominated Responses

Allergy and Dermatophytes

Dermatophytosis

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