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Most modern research into the immune effects of breast milk has focused on the impacts of immunoglobulin or oligosaccharide content. However, immediately prior to parturition, the cell populations of breast milk become selectively enriched for CD8+ T cells of an effector memory subtype. Despite this observation that the cellular content of breast milk contains a distinct leukocyte population when compared to peripheral blood, the physiologic role of these CD8+ effector memory cells is unknown. Research encompassing animal models and humans has demonstrated that leukocytes are capable of transferring antigen-specific immunity even when lysed, dialyzed to enrich for fractions less than 10 kDa, and orally administered. Our previous work built upon these reports to elucidate several aspects of this dialyzable leukocyte extract (DLE) activity: only DLE from T effector memory CD8+ cells was capable of transferring antigen-specific immunity; the DLE activity was TCRβ dependent; dendritic cells (DCs) were the cellular target of DLE; and DLE enhanced immune activity in epithelial challenge models via induction of IL-6 from DCs. Herein, we reveal that breast milk dialysate activates similar cytokine and genetic pathways as DLE taken from peripheral blood and murine spleens through TCRβ- and CD8-dependent mechanisms. These findings suggest that the CD8+ memory T cells enriched in breast milk, even after potential lysis in the infant gut, may represent a mechanism for passive transfer of cellular immunity from mother to child., (©2020 Society for Leukocyte Biology.)

Cellular lysates from PPD + donors have been reported to transfer tuberculin reactivity to naïve recipients, but not diphtheria reactivity, and vice versa. A historically controversial topic, the terms "transfer factor" and "DLE" were used to characterize the reactivity-transferring properties of lysates. Intrigued by these reported phenomena, we found that the cellular extract derived from antigen-specific memory CD8 + T cells induces IL-6 from antigen-matched APCs. This ultimately elicits IL-17 from bystander memory CD8 + T cells. We have identified that dialyzable peptide sequences, S100a9, and the TCR β chain from CD8 + T cells contribute to the molecular nature of this activity. We further show that extracts from antigen-targeted T cells enhance immunity to Staphylococcus aureus and Candida albicans These effects are sensitive to immunization protocols and extraction methodology in ways that may explain past discrepancies in the reproducibility of passive cellular immunity., (© Society for Leukocyte Biology.)

Immunostimulatory sequence (ISS) DNA containing unmethylated CpG dinucleotides stimulate NK and APC to secrete proinflammatory cytokines, including IFN-alphabeta and -gamma, TNF-alpha, and IL-6 and -12, and to express costimulatory surface molecules such as CD40, B7-1, and B7-2. Although ISS DNA has little direct effect on T cells by these criteria, immunization of wild-type mice with ISS DNA and OVA results in Ag-specific CTL and Th1-type T helper activity. This investigation examines the mechanisms by which ISS DNA primes CD8(+) and CD4(+) lymphocyte activities. In this report we demonstrate that ISS DNA regulates the expression of costimulatory molecules and TAP via a novel autocrine or paracrine IFN-alphabeta pathway. Coordinated regulation of B7 costimulation and TAP-dependent cross-presentation results in priming of Ag-specific CD8(+) CTL, whereas CD40, B7, and IL-12 costimulation is required for priming of CD4(+) Th cells by ISS-based vaccines.