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+ naïve 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 α-, β- and ĸ-casein and β-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 ĸ-casein which were restored after Treg depletion. Interleukin-4 and interferon-γ 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 α-, β- and ĸ-caseins (but not β-lactoglobulin) were observed in clinically reactive IgE-mediated CMA patients only. A markedly decreased proliferative response to ĸ-casein in tolerised IgE-mediated CMA patients with atopic dermatitis, which was abrogated by Treg depletion, suggested a role for ĸ-casein in tolerance induction. Non-IgE-mediated CMA patients had no increased proliferative response to any milk proteins.

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