CD8 Reactivity to Microorganisms in Blood and 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 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.

-INCLUSION CRITERIA:

1. Age 18+ years.

2. Willing to allow storage of blood, breast milk, and cells for future research.

3. Willing to have genetic testing performed.

4. Meets one of the 3 following criteria:

1. Confirmed exposure:

-Exposure has been verifiably documented (eg, receiving an immunization or DNCB
sensitization treatment).

OR

-Clinical history is consistent with established epidemiology of the microbe of
interest (eg, documentation of past infection; or to a lesser priority travel to
endemic areas or living with an individual that suffers from chronic infection
with the targeted microbe).

AND

-Positive results on established clinical immunity tests (eg, viral RNA, antibody
titers, etc).

2. Suspected exposure: Clinical history is consistent with established epidemiology
of the microbe of interest (eg, travel to endemic areas, documentation of past
infection) but no established clinical assay exists to verify exposure.

3. Non-exposed: Absence of exposure to targeted microorganisms as measured by lack
of exposure to infected individuals, lack of travel to endemic areas, no
immunization history, negative screening tests, or other methods of establishing
exposure history to mucosal microbial agents.

EXCLUSION CRITERIA:

1. Active use of immunosuppressive medications.

2. Any condition that, in the opinion of the investigator, contraindicates participation
in this study.