Ana o 1 and Ana o 2 cashew allergens share cross-reactive CD4(+) T cell epitopes with other tree nuts.

BACKGROUND: Allergies to cashew are increasing in prevalence, with clinical symptoms ranging from oral pruritus to fatal anaphylactic reaction. Yet, cashew-specific T cell epitopes and T cell cross-reactivity amongst cashew and other tree nut allergens in humans remain uncharacterized. OBJECTIVES: In this study, we characterized cashew-specific T cell responses in cashew-allergic subjects and examined cross-reactivity of these cashew-specific cells towards other tree nut allergens. METHODS: CD154 up-regulation assay was used to determine immunodominance hierarchy among cashew major allergens at the T cell level. The phenotype, magnitude and functionality of cashew-specific T cells were determined by utilizing ex vivo staining with MHC class II tetramers. Dual tetramer staining and proliferation experiments were used to determine cross-reactivity to other tree nuts. RESULTS: CD4(+) T cell responses were directed towards cashew allergens Ana o 1 and Ana o 2. Multiple Ana o 1 and Ana o 2 T cell epitopes were then identified. These epitopes elicited either TH 2 or TH 2/TH 17 responses in allergic subjects, which were either cashew unique epitope or cross-reactive epitopes. For clones that recognized the cross-reactive epitope, T cell clones responded robustly to cashew, hazelnut and/or pistachio but not to walnut. CONCLUSIONS: Phylogenetically diverse tree nut allergens can activate cashew-reactive T cells and elicit a TH 2-type response at an epitope-specific level. CLINICAL RELEVANCE: Lack of cross-reactivity between walnut and cashew suggests that cashew peptide immunotherapy approach may not be most effective for walnut.

Effect of IL-2 on immunoglobulin production by anti-CD40-activated human B cells: synergistic effect with IL-10 and antagonistic effect with IL-4.

Activation of B cells by anti-CD40 provides an excellent model to investigate the direct effect of various cytokines on Ig production. Using this culture system, we examined the effect of IL-2 alone or in combination with other cytokines. IL-2 alone had only a moderate effect on Ig production by anti-CD40-activated B cells if compared with the effect of IL-10. However, IL-2 significantly augmented the synthesis of IgM, IgA, and IgG, including all IgG subclasses by anti-CD40-activated B cells cultured in the presence of IL-10. Both IgD- and IgD+ B cells showed an increase of IL-10-induced Ig production if IL-2 was added to the culture. The addition of IL-2 also increased immunoglobulin synthesis by anti-CD40/IL-10-activated B cells from patients with common variable immunodeficiency (CVI) and defective IL-2 production, suggesting that in a subgroup of CVI patients the IL-2 deficiency may contribute to the observed hypogammaglobulinemia. In contrast, the addition of IL-2 had a suppressive effect on IgE and IgG4 production by B cells cultured in the presence of anti-CD40 and IL-4. These data demonstrate that IL-2 plays an active role in the regulation of Ig production via CD40 by anti-CD40-activated B cells.

The role of adhesion molecules in the regulation of antibody responses.

We used the T-cell-dependent antigen, bacteriophage (phage) phi X174, to study antibody synthesis in patients, guinea pigs, and dogs with complement component deficiencies (C2, C4, C3, C7); in patients with adhesion molecule deficiencies (CD11/CD18 or sialylated Lewisx); and in patients with the hyper IgM (HIM) syndrome (absence of functional gp39 expression by activated T cells). Patients and guinea pigs deficient in early complement components, patients deficient in CD11/CD18, and patients lacking functional gp39 on activated T cells responded to repeated phage immunizations with depressed antibody titers, lack of or inadequate amplification, and failure to switch from IgM to IgG, suggesting that defective T-cell-B-cell interaction is the cause of the antibody deficiency observed in these patients.

Eosinophilic fasciitis in children frequently progresses to scleroderma-like cutaneous fibrosis.

We evaluated longterm outcome in 21 pediatric patients with biopsy proven eosinophilic fasciitis (EF), 4 followed in our rheumatology clinic and 17 reported in the literature. Two-thirds of these patients developed residual cutaneous fibrosis, while one-third enjoyed complete resolution of disease. Children under age 7 years were twice as likely as those over age 7 years to experience disease progression to cutaneous fibrosis [relative risk = 2.0 (95% confidence intervals 1.2, 3.4)]. Fourteen of 17 patients with extensive disease at diagnosis (involvement of 3-4 extremities +/- trunk) progressed to cutaneous fibrosis whereas all 4 patients with minimal disease (involvement of 1-2 extremities) at onset resolved completely. We detected no association between progression to cutaneous fibrosis and sex of patient, duration of symptoms prior to therapy, type of therapy, history of prior physical stress, or laboratory variables at diagnosis.