Memory T cell proliferation in cow's milk allergy after CD25+ regulatory T cell removal suggests a role for casein-specific cellular immunity in IgE-mediated but not in non-IgE-mediated cow's milk allergy

Background: Previously reported increased lymphocyte proliferative responses in cow's milk allergy (CMA) may have been influenced by the lipopolysaccharides (LPS) which contaminate most commercial cow's milk protein (CMPs). Moreover, peripheral blood mononuclear cells (PBMC) contain both B cells, CD45RA+ naive T cells, CD25+ regulatory T cells (Tregs) in addition to antigen-specific CD45RA-memory T cells. Methods: PBMC from clinically reactive and tolerised patients with IgE- and non-IgE-mediated CMA were depleted of CD45RA+ T cells and putative CD25+ Tregs. The proliferative index to LPS-depleted alpha-, beta- and kappa-casein and beta-lactoglobulin was compared in the memory T-cell-enriched, Treg-depleted PBMC and in bulk PBMC. Results: Clinically reactive IgE- mediated CMA patients had increased responses to caseins only. Tolerised patients, particularly those with atopic dermatitis, had decreased responses to kappa-casein which were restored after Treg depletion. Interleukin-4 and interferon-gamma were generally not detected in the culture supernatants. No differences were seen between reactive and tolerant delayed non-IgE-mediated CMA patients. Conclusions: Proliferative responses to alpha-, beta- and kappa-caseins (but not beta-lactoglobulin) were observed in clinically reactive IgE-mediated CMA patients only. A markedly decreased proliferative response to kappa-casein in tolerised IgE-mediated CMA patients with atopic dermatitis, which was abrogated by Treg depletion, suggested a role for kappa-casein in tolerance induction. Non-IgE-mediated CMA patients had no increased proliferative response to any milk proteins. Copyright (c) 2007 S. Karger AG, Basel.