CD8 Reactivity to Microorganisms in Blood and Breast Milk

Immune Modulation, Leprosy, Lyme Disease, Pertussis, Tuberculosis

Infectious Diseases, Dendritic Cells, Pathogens, Passive Cellular Immunity

Background: When a person is exposed to something that causes an infection, the body sends a type of cell called CD8 T cells to attack it. Those cells are also found in breast milk. Nursing mothers pass these cells to their child, which helps the child fight infections, too. Researchers want to learn more about how CD8 cells work to keep people healthy. Objective: To learn more about how the human body fights off infections. Eligibility: People age 18 years and older who either have an infection, are suspected to have an infection, or recently got a vaccine. The household contacts of these people and people who have not been recently exposed to any infection are also needed. Design: Participants will be screened with a medical and health history and physical exam. They may have blood tests. The first study visit can be the same day as screening. It can be up to 3 months later. For those visits, screening tests will be repeated. At the first visit, participants will have blood collected from an arm vein. Participants who are breastfeeding may provide a small sample of breast milk. They may collect it at home or bring a pumping device to NIH to collect it. NIH can also provide a breast pump. Participants may be contacted for up to 1 year after the first visit to give samples of blood and/or breast milk. Up to 4 additional visits, which will each take about 1 hour, may be scheduled. A personal physician or local lab can collect blood from participants and ship it to NIH. Breast milk cannot be shipped.

Cellular lysates from purified protein derivative-positive donors have been reported to transfer tuberculin reactivity to na(SqrRoot) ve recipients, but not diphtheria reactivity; similarly, cell lysates from diphtheria-reactive donors appear to transfer diphtheria reactivity without impacting responses to tuberculin. A historically controversial topic, the terms transfer factor and dialyzed leukocyte extract were used to characterize the reactivity-transferring properties of lysates. We found that the cellular extract derived from antigen-specific memory CD8+ T cells induces interleukin (IL)-6 from antigen-matched antigen-presenting cells. This ultimately elicits IL-17 from bystander memory CD8+ T cells. We identified that dialyzable peptide sequences, S100a9, and the TCR \<= chain from CD8+ T cells contribute to the molecular nature of this activity. We further showed that extracts from antigen-targeted T cells enhance immunity to Staphylococcus aureus and Candida albicans. The observed anti-Candida activity of lysates was enhanced when the cells were taken from individuals with higher-than-average exposure to Candida and correlated with increased numbers of Candida-reactive T-cells. These effects are sensitive to immunization protocols and extraction methodology in ways that may explain past discrepancies in the reproducibility of passive cellular immunity. Work by other groups has revealed that memory CD8+ T cells are also the only cell population enriched in breast milk as compared to an equal volume of peripheral blood. Taken together, it may be that the CD8+ memory T cells in breast milk serve as a mechanism of passive cellular immunity transference from mother to offspring. We thus aim to expand our analysis into the potential that lysates taken from sources with enriched immunity against a given microorganism will induce greater in vivo and mouse model activity compared to lysates from non-immune sources, and that this difference in lysate activity will be directly related to the CD8+ T cell enrichment. In this study, we will collect blood and/or breast milk samples from donors with known or suspected exposure to pathogens, and also from healthy non-exposed volunteers. Research evaluations of samples will be done for the relevant microbe(s) of interest. The volume of blood taken from lacting mothers will be limited to 20mL or less per visit. Cells may be proliferated, immortalized, lysed and dialyzed, and/or stored. Cellular lysates will subsequently be used in both in vitro and pre-clinical animal models to assess for therapeutic potential.

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