Candidin and trichophytin stimulate the production of Th1 and regulatory cytokines by peripheral blood mononuclear cells: implication for their use as adjuvants in immunotherapy.

AIM: This study's objective was to investigate whether candidin or trichophytin elicit recall immune responses that could potentially inhibit a Th2 response. MATERIALS & METHODS: Peripheral blood mononuclear cells from nine allergic and seven nonallergic individuals were cultivated in vitro in the presence or absence of these fungal extracts. RESULTS: Trichophytin or candidin, or both, stimulated the production of regulatory cytokines (TGF-ß and/or IL-10), accompanied or not by stimulation of production of cytokines associated with the Th1 response (TNF-α, IL-12 and IFN-γ), but without stimulation of Th2 cytokines (IL-5 and IL-13) and IL-17, by peripheral blood mononuclear cells of most allergic and nonallergic individuals. CONCLUSION: These results indicate that these fungal extracts could be used as adjuvants in personalized therapeutic vaccines in a fair proportion of individuals. In addition, they justify the carrying out of investigations aimed at identifying molecules in these extracts that might exclusively induce Treg and/or Th1 immune responses.

[Anti-fungal drug liranaftate suppresses fungal element-promoted production of IL-8 in normal human keratinocytes].

Dermatophytes reside in the stratum corneum of the epidermis, and one scenario in superficial dermatophytosis is that fungi stimulate keratinocytes to secrete chemokines, thereby attracting inflammatory cells. We investigated the effect of the cytokine / chemokine production of keratinocytes solely stimulated by fungal elements. The fungal elements beta-D-glucan and trichophytin from Trichophyton rubrum and Trichophyton mentagrophytes augmented production of IL-8 and IL-1 alpha of cultured normal human epidermal keratinocytes. It was found that keratinocytes can recognize elements of dermatophytes as a pathogen. Next we examined the effect of liranaftate, a representative Japanese thiocarbamate antifungal agent, on the production of IL-8 and IL-1 alpha. Keratinocytes were incubated with this antifungal drug in the presence of beta -glucan or trichophytin. Augmented production of IL-8 was profoundly suppressed by the addition of liranaftate to the culture in a dose-dependent manner. Clinically, liranaftate an antifungal drug with IL-8-decreasing activity may reduce infiltration of neutrophils in the skin and their invasion into the epidermis.

Cytokine production of peripheral blood mononuclear cells in a dermatophytosis patient in response to stimulation with trichophytin.

Interferon-gamma (IFN-gamma), interleukin 2 (IL-2) and granulocyte/macrophage colony-stimulating factor (GM-CSF) were detected in the culture supernatant after 72 hours incubation with trichophytin in the peripheral blood mononuclear cells (PBMC) obtained from a patient who had a dermatophyte infection. These findings indicate that this patient has peripheral T-lymphocytes that produced IFN-gamma, IL-2 and GM-CSF, which may play roles in the development of delayed-type hypersensitivity (DTH) reaction in the skin.

Dermatofitides: estado atual dos conhecimentos / Dermatophytids: current status

Os autores apresentam um estudo retrospectivo de 58 pacientes com tinea pedis e dermatofítide de mäos. Neste grupo de pacientes, o fungo mais vezes isolado, dos pés, foi Trichophyton mentagrophytes (50 casos, 88,2%). A propósito do tema, fazem uma revisäo atualizada da bibliografia médica. Discute-se, em particular, o valor da intradermorreaçäo com tricofitina, como um dos critérios adotados para firmar o diagnóstico de mícide. É dada ênfase a necessidade de se obter antígeno purificado, para se poder valorizar a prática do teste

Purified trichophytin: lymphocyte reactivity in vitro and trichophytin-induced suppression.

Three trichophytin preparations from different strains of Trichophyton mentagrophytes were produced according to the ethylene glycol method and assessed for their lymphocyte stimulation activity in vitro (LST). These trichophytin preparations showed significant variations in their effects on cord lymphocytes reactivity. The preparations also varied in their stimulation of lymphocytes from patients with dermatophytosis. Conclusions could be drawn about the immunological specificity, sensitivity and lymphocyte toxicity, which is important for the standardization of antigens. Furthermore, it was demonstrated that trichophytin-preincubated lymphocytes mediated a suppression of lymphocyte reactivity to this antigen.

Immunological aspects of dermatophyte infections in hereditary palmo-plantar keratoderma.

Family and personal histories of atopy, total IgE level in serum, AB0 blood groups, trichophytin reactions, IgE RAST, IgG RAST and precipitating antibodies were investigated in patients with hereditary palmo-plantar keratoderma and dermatophytosis. 44% of the patients with dermatophytosis had a personal and/or family history of atopy and 67% a total IgE greater than 100 kU/ml. No significant differences in the rate of dermatophytosis were found between atopics and non-atopics, nor were there differences between patients with a total IgE above and those with a level below 100 kU/ml. The determination of AB0 blood groups showed that T. mentagrophytes occurred significantly more often in patients with blood group A. All delayed trichophytin reactions were negative. A positive immediate trichophytin reaction was found in only 1 patient, who also had a raised level of IgE antibodies against dermatophytes. The level of specific IgG antibodies was increased in patients infected with T. rubrum and E. floccosum, which two species were found to have at least one antigen in common. Homologous precipitating antibodies occurred in 54% of the patients with hereditary palmo-plantar keratoderma, which is a considerably higher value than that reported in dermatophyte infected patients without this inherited disorder.

The local xenogeneic graft-versus-host reaction as a clinical test for immunocompetence of human T lymphocytes.

Studies carried out in our laboratory during the years indicated that the local xenogeneic graft-versus-host reaction (GVHR) might serve as a useful clinical assay of the immunocompetence of human T lymphocytes. Additional studies were therefore carried out using purified populations of B, T and null cells as well as normal mononuclear cell populations, so as to determine the nature of the cells responsible for induction of the reaction and further delineate the factors capable of modifying this pattern of reactivity. Populations of T cells alone gave the largest reaction whereas both B cells from patients with chronic lymphatic leukemia and null cells from patients with acute lymphatic leukemia failed completely to induce a GVHR. The addition of anti-T-lymphocytic serum abolished the reaction, providing further proof of the role played by T lymphocytes. Thymic hormone (THF) was found to enhance the reaction when applied both in vivo and in vitro. The immunostimulatory agents transfer factor and levamisole also enhanced the GVHR obtained with normal mononuclear cells. Cytoxan was found to have an enhancing effect at low doses and an inhibiting effect at high doses. Trypsin also acted to abolish the GVHR. The combination of two populations of normal mononuclears always gave a larger GVHR, indicating allogeneic antigen stimulation. Depletion of the monocytes from the population of normal mononuclears resulted in a smaller reaction, providing further evidence that monocytes are required for T-lymphocyte antigen-induced reactivity. On the basis of these findings it is proposed that the local xenogeneic GVHR is a useful clinical test for the measurement of immunocompetence of T lymphocytes, for the differential diagnosis of leukemias and for the determination of the effectiveness of THF.