Measurement of T-Cell-Derived Antigen Binding Molecules and Immunoglobulin G Specific toCandida albicansMannan in Sera of Patients with Recurrent Vulvovaginal Candidiasis

Abstract

Immunoglobulin G (IgG) and T-cell-derived antigen binding molecules (TABM) specific to whole Candida extract and to Candida-derived mannans prepared by both the cetryltrimethylammonium bromide (CTAB) and alkaline degradation (PEAT) methods were measured in the sera of women with vulvovaginal candidiasis and controls. In the patients there were significantly higher levels of IgG to both CTAB and PEAT mannans and of TABM to CTAB mannan. TABM specific to CTAB mannan was purified from the serum of a patient with a high titer of this TABM. The purified TABM bound specifically to CTAB mannan and to other yeast and mold extracts. This TABM preparation was associated with transforming growth factor ␤2 (TGF-␤2), and on specific binding to mannan there was a marked increase in the level of detectable TGF-␤2. This increase in TGF-␤2 level was critically dependent on the relative concentrations of the purified TABM and mannan, being smallest when either was in excess. The TABM specific to CTAB mannan was also shown to inhibit Candida-stimulated gamma interferon production. The results suggest that CTAB mannan-specific TABM may increase susceptibility to vulvovaginal candidiasis in association with a shift in the immune response to the Th2 type.

Increased Levels ofCandida albicansMannan-Specific T-Cell-Derived Antigen Binding Molecules in Patients with Invasive Candidiasis

“…In addition, we previously found that CAM-stimulated PBMCs of AEDS patients produced more IFN-␥ and IL-2 than those of healthy controls (43), indicating elevated Th1-type immunity. Unlike in the earlier study by Little et al (25), we noticed no difference between the CAM-TABM levels of RVVC patients and those of the controls in the present work, which probably resulted from the use of different patient material. The previous findings of cellular immunity in patients with RVVC have been controversial: after C. albicans stimulation, decreased (3,6), similar (8), or increased (34) levels of lymphoproliferation and IFN-␥ production of the PBMCs of RVVC patients compared with those of the PBMCs of controls were suggested.…”

“…These include C. albicans mannanTABMs (CAM-TABMs) in recurrent vulvovaginal candidiasis (RVVC) and inflammatory bowel syndrome (24,25); casein-, ␤-lactoglobulin-and ␣-lactalbumin-specific TABMs in milk intolerance (26); benzoic acid-TABMs in toluene sensitivity (18); and filarial extract-TABMs in chronic filariasis (24). All these TABMs were shown to carry the same epitope (3C9) detected by a monoclonal anti-TABM antibody, MG3C9-1A12 (24).…”

“…TABMs specific for Cetavlon-purified mannan polysaccharide of C. albicans (CAM-TABMs) were characterized by Little et al (25). They proved cross-reactive because they also bound to C. albicans whole extract and other fungi, including Malassezia.…”

Cell and antibody mediated immunity induced by vaccination with novel Candida dubliniensis mannan immunogenic conjugate

“…The diversity of the CD4 + and CD8 + T-cell responses could be seen in different mechanisms through which T cells participate in the control of fungal infections [41]. CD4 + T cells have been found to secrete soluble, T-cell-derived antigen binding molecules (TABMs), mannan-specific TABMs were found in patients with invasive candidiasis [42,43]. Recently, there was evidence that the ability of CD4 + T cells to provide effective support for the generation of optimal memory CD8 + T-cell population is a highly regulated process, not random cell-cell interactions [44].…”

Distinct Protective Host Defenses against oral and vaginal Candidiasis

“…However, elevated levels of MCP-1 did not result in any demonstrable increases in T cells or macrophages in vaginal lavage uid (previously shown as well in vaginal tissue [61]). Interestingly, although not yet identi ed in vaginal secretions, a T cell derived antigen-binding molecule (TABM) has been identi ed in serum of RVVC patients, and to a lesser extent in control subjects, that can become associated with TGF-b and inhibit Candida-speci c PBL proliferation and cytokine production [74]. When local Th1/Th2 cytokines were evaluated, high constitutive levels of transforming growth factor-beta (TGF-b ) were found whereas other Th1/Th2 cytokines (i.e., IL-2, IFN-g , IL-12, IL-4, IL-10) were low or undetectable [72].…”