Increased levels of Candida albicans mannan-specific T-cell-derived antigen binding molecules in patients with invasive candidiasis.

In addition to cytokines, CD4+ T cells have been found to secrete soluble, T-cell-derived antigen binding molecules (TABMs). These antigen-specific immunoproteins are thought to have immunoregulatory properties in the suppression of cell-mediated immunity (CMI) because they often associate with interleukin-10 (IL-10) and transforming growth factor beta. Decreased CMI causes susceptibility to infections caused by organisms which are normally nonpathogenic. In this situation, e.g., Candida albicans saprophytism may develop into invasive candidiasis. The difficult diagnosis of invasive candidiasis is based on the findings obtained from blood cultures and with tissue biopsy specimens, with some additional diagnostic value gained by the detection of Candida albicans mannan antigenemia and antimannan antibodies. In the present study, Candida albicans mannan-specific TABM (CAM-TABM) levels in the sera of patients with invasive candidiasis (n = 11), Candida colonization (n = 11) and noncolonization (n = 10), recurrent vulvovaginal candidiasis (n = 30), and atopic eczema dermatitis syndrome (n = 59) and healthy controls (n = 30) were analyzed. For 14 participants, the effect of mannan stimulation on TABM production and gamma interferon (IFN-gamma) and IL-4 mRNA expression by peripheral blood lymphocytes was also studied. It was demonstrated that CAM-TABM production was the highest in patients with invasive candidiasis and that CAM-TABM levels could distinguish Candida-colonized patients from noncolonized patients. In addition, the CAM-TABM level was directly related to mRNA expression for IL-4 but not IFN-gamma. These results reinforce the view that TABMs are associated with decreased CMI, immunoregulation, and the T-helper cell 2-type immune response.

Candida albicans-specific lymphoproliferative and cytokine (IL-4 and IFN-gamma) responses in atopic eczema dermatitis syndrome. Evidence of CD4/CD8 and CD3/CD16+CD56 ratio elevations in vitro.

BACKGROUND: Hypersensitivity to cross-reactive mannan polysaccharide allergens of saprophytic yeasts is likely to be involved in the pathogenesis of atopic eczema dermatitis syndrome (AEDS). Mannans induce elevated specific immunoglobulin E and lymphoproliferative responses in peripheral blood mononuclear cells (PBMCs). To gain more detailed data of the involvement of different subpopulations of PBMCs in AEDS after mannan stimulation, changes in the cell-surface marker distribution were analysed. METHODS: The Ficoll-isolated PBMCs of eight yeast hypersensitive AEDS patients and seven non-AEDS controls were stimulated in vitro by mannan (CAM) or whole extract antigen [In-House Reference (IHR)] of Candida albicans or tuberculin [purified protein derivative (PPD)] and after immunofluorescence staining analysed by flow cytometry. The expression of cytokine mRNA was measured by kinetic real-time polymerase chain reaction (TaqMan). RESULTS: After 7-day antigen stimulation, there were significant increases in the CD3/CD16(+)CD56 ratio (P = 0.028 with mannan and P = 0.006 with IHR), CD4/CD8 ratio (P = 0.049 with mannan) and interleukin-4/interferon-gamma (IL-4/IFN-gamma) mRNA ratio (P = 0.028 with IHR) and a decrease in the CD3/CD19 ratio (P = 0.035 with mannan) of AEDS patients' PBMCs as compared with healthy controls' cells. These changes were not seen in cultures with PPD. CONCLUSIONS: The observed CAM and IHR-induced elevations in T cell/natural killer cell, CD4/CD8 and IL-4/IFN-gamma ratios suggest that C. albicans-induced TH(2)-type responses can also play a role in AEDS.