Human dermatophyte‐responsive T‐cell lines recognize cross‐reactive antigens associated with mannose‐rich glycoproteins

Abstract

Resistance to dermatophyte infections has been shown to be mediated in part by T lymphocytes. The dermatophyte antigens recognized by human T lymphocytes and their degree of cross-reactivity were analyzed. Dermatophyte-responsive T-cell lines were generated by in vitro sensitization to crude fungal extracts obtained from Trichophyton rubrum, Trichophyton tonsurans, Microsporum canis and Epidermophyton floccosum. Proliferation was measured by incorporation of 3H-thymidine. The human T-cell lines responded to fungal extracts derived from these various dermatophyte species, demonstrating the recognition of cross-reactive antigens by human T cells. However, the T cells were dermatophyte-specific as they did not respond to herpes antigen, nor did herpes-specific T cells derived from the same donors respond to dermatophyte antigens. The mannose-rich glycoprotein fraction (mannan) isolated from T. rubrum was able to induce proliferation of T-cell lines generated by stimulation with various fungal extracts. Furthermore, a T-cell line generated by stimulation with mannan derived from T. rubrum proliferated in response to extracts from various fungal species, indicating that a major cross-reactive dermatophyte T-cell antigen was present in the mannose-rich glycoprotein fraction.

CD4+ and CD8+ T cells mediated direct cytotoxic effect against Trichophyton rubrum and Trichophyton mentagrophytes

“…This finding is in accordance with previous studies demonstrating that T. rubrum can produce substances that diminished the immune response 42–44 . Therefore T. rubrum is one of the most common causes of dermatophytosis in humans, accounting for more than 90% of chronic human’s cases 1 .…”

Onychomycosis: clinical perspective

“…23 The potential iatrogenic and immunologic implications of onychomycosis, carrying a large fungal load, remains to be investigated; however, it has been reported that T. rubrum infection may suppress cell‐mediated immunity. 24–26 Onychomycosis has a particular impact on certain population groups such as the elderly, HIV‐infected patients, 27–30 and in those with concomitant diabetes mellitus. 31 Onychomycosis patients harbor a large fungal load and from an epidemiologic viewpoint may be a source of infection for other people as well as for reinfection for tinea manuum and pedis.…”

“… 25 Trichophytin can elicit a specific lymphoproliferative response, although it yields predominantly T‐suppressor cells. 26 Although cell‐mediated immune reactions may be suppressed by T. rubrum , the humoral response generally remains intact and antibodies of different classes have repeatedly been demonstrated. Recently, Trichophyton ‐specific immunoglobulin E (IgE) antibodies were found in patients with T. rubrum infections.…”

Combating Fungal Infections

“…In a dose-dependent manner, TRM are able to inhibit in vitro lymphoproliferative response of mononuclear leukocytes in response to several antigens (dermatophytic or not) and mitogens (Blake et al 1991a, b); paradoxically, they are a major T-cell antigen (MacCarthy et al 1994). They include lymphocyte inhibition by cell-wall mannans, macrophage function alteration, differential activation of keratinocytes and, putatively, differential secretion of proteases.…”