Donor-derived regulatory dendritic cell infusion modulates effector CD8+ T cell and NK cell responses after liver transplantation.

Immune cell-based therapies are promising strategies to facilitate immunosuppression withdrawal after organ transplantation. Regulatory dendritic cells (DCreg) are innate immune cells that down-regulate alloimmune responses in preclinical models. Here, we performed clinical monitoring and comprehensive assessment of peripheral and allograft tissue immune cell populations in DCreg-infused live-donor liver transplant (LDLT) recipients up to 12 months (M) after transplant. Thirteen patients were given a single infusion of donor-derived DCreg 1 week before transplant (STUDY) and were compared with 40 propensity-matched standard-of-care (SOC) patients. Donor-derived DCreg infusion was well tolerated in all STUDY patients. There were no differences in postoperative complications or biopsy-confirmed acute rejection compared with SOC patients up to 12M. DCreg administration was associated with lower frequencies of effector T-bet+Eomes+CD8+ T cells and CD16bright natural killer (NK) cells and an increase in putative tolerogenic CD141+CD163+ DCs compared with SOC at 12M. Antidonor proliferative capacity of interferon-γ+ (IFN-γ+) CD4+ and CD8+ T cells was lower compared with antithird party responses in STUDY participants, but not in SOC patients, at 12M. In addition, lower circulating concentrations of interleukin-12p40 (IL-12p40), IFN-γ, and CXCL10 were detected in STUDY participants compared with SOC patients at 12M. Analysis of 12M allograft biopsies revealed lower frequencies of graft-infiltrating CD8+ T cells, as well as attenuation of cytolytic TH1 effector genes and pathways among intragraft CD8+ T cells and NK cells, in DCreg-infused patients. These reductions may be conducive to reduced dependence on immunosuppressive drug therapy or immunosuppression withdrawal.

Rats assess degree of relatedness from human odors.

Despite widespread interest in the evolutionary implications of human olfactory communication, the mechanisms underlying human odor production are still poorly understood. Previous studies have demonstrated that human odor cues are related to variations in the major histocompatibility complex, but it is unclear whether odors are associated with overall genotypic variation. In this study, we investigated whether more closely related humans produce more similar odor cues. To assess objective odor qualities we tested odor similarity using rats in a habituation-discrimination paradigm. Rats were first habituated to a referent human odor and were then presented with two test odors obtained from individuals related in different degrees to the referent. Investigation times for each odor were compared. Because rats investigate novel odors longer than familiar odors, we were able to determine which test odor the rats perceived as more similar to the referent human odor. For six of ten odor donor families, rats investigated the odor of the less closely related individual significantly longer than that of the more closely related individual, and investigation durations were in the expected direction for all families. These results indicate that similarity of human odor cues is associated with degree of genetic relatedness, with more closely related humans producing more similar odor cues. This study supports the hypothesis that odor cues provide information regarding degree of relatedness and may thus affect a wide variety of human behaviors, including kin preferences, nepotism, and mate choice.

Different patterns of contingent stimulation differentially affect attention span in prelinguistic infants.

The ability to sustain attention influences different domains including cognitive, motor, and communicative behavior. Previous research has demonstrated how an infant's parent can influence sustained attention. The purpose of our study was to expose infants systematically to both sensitive and redirective patterns of behavior to examine how unfamiliar individuals could influence attention. Results revealed infants changed their patterns of looking with the unfamiliar individuals. Infants had longer durations of sustained attention when interacting with a sensitive unfamiliar individual who followed into their attentional focus as opposed to an intrusive person who led their attentional focus. This study demonstrates that infants discriminate patterns of contingency to persons seen for only a short period of time broadening the range of potential mentors for learning.