Clinical Trial: CD8 Reactivity to Microorganisms in Blood and Breast Milk

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: CD8 Reactivity to Microorganisms in Blood and Breast Milk

Brief Summary:

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.

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
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome: To compare the in vitro and mouse model immune stimulatoryproperties of lysates derived from microbe-specific CDB+ T cellenriched sources. [ Time Frame: There are no definitive time points in this sample collection study ]

Original Primary Outcome: Same as current

Current Secondary Outcome: To compare how the in vitro and mouse model immune stimulatoryproperties of breast milk vary with the microbe specific CDB+ T cellconcentration. [ Time Frame: There are no definitive time points in this sample collection study ]

Original Secondary Outcome: Same as current

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: March 15, 2017
Date Started: March 28, 2017
Date Completion: March 31, 2022
Last Updated: May 12, 2017
Last Verified: March 8, 2017