Intestinal CD8+ T cell responses are abundantly induced early in human development but show impaired cytotoxic effector capacities.

Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8+ T cells are critical to achieve viral control. However, studies investigating the development of CD8+ T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8+ T cell compartment in human fetal, infant and adult intestinal tissues. CD8+ T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7-CD45RA-CD127-KLRG1+/- CD8+ T cells compared to tissue-resident memory CD69+CD103+CD8+ T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8+ T cells was, however, markedly reduced compared to adult intestinal CD8+ T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8+ T cells. Taken together, we demonstrate that intestinal CD8+ T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8+ T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.

Neuroendocrine-immune interaction in fish: differential regulation of phagocyte activity by neuroendocrine factors.

Coping with physical, chemical and biological disturbances depends on an extensive repertoire of physiological, endocrinological and immunological responses. Fish provide intriguing models to study bi-directional interaction between the neuroendocrine and the immune systems. Macrophages and granulocytes are the main actors in the first and rapid innate immune response. They are resident in different organs and are moreover rapidly recruited and activated upon infection. They act in response to recognition of pathogen-associated molecular patterns (PAMPs) via a repertoire of surface and intracellular receptors by inducing a plethora of defense reactions aiming to eradicate the pathogen. Subsequent production of inflammatory mediators stimulates other leukocytes required to develop an adaptive and specific antibody response. The type of phagocyte reaction will therefore depend on their differentiation state, specific receptor repertoire and their specific location. Apart from these pathogen induced responses, immune reactivity may be modulated by neuroendocrine factors. Over the last years we extensively studied changes in carp stress axis activity and the effect of its end-products on the immune system in an acute stress paradigm. We focus on specific neuroendocrine receptors on leukocytes and their effect on crucial phagocyte activities. We performed identification and functional analyses of different glucocorticoid, opioid and adrenergic receptors on carp phagocytes. Results show that their ligands of neuroendocrine origin may have substantial impact on specific phagocyte functions in a differential way. Inflammatory and microbicidal responses fight pathogens but may be detrimental to the host tissue. Neuroendocrine modulation may regulate inflammation to reach an optimum defense while preventing excessive host cell damage.

Characterization of Gordonia sp. strain F.5.25.8 capable of dibenzothiophene desulfurization and carbazole utilization.

A dibenzothiophene (DBT)-degrading bacterial strain able to utilize carbazole as the only source of nitrogen was identified as Gordonia sp. F.5.25.8 due to its 16S rRNA gene sequence and phenotypic characteristics. Gas chromatography (GC) and GC-mass spectroscopy analyses showed that strain F.5.25.8 transformed DBT into 2-hydroxybiphenyl (2-HBP). This strain was also able to grow using various organic sulfur or nitrogen compounds as the sole sulfur or nitrogen sources. Resting-cell studies indicated that desulfurization occurs either in cell-associated or in cell-free extracts of F.5.25.8. The biological responses of F.5.25.8 to a series of mutagens and environmental agents were also characterized. The results revealed that this strain is highly tolerant to DNA damage and also refractory to induced mutagenesis. Strain F.5.25.8 was also characterized genetically. Results showed that genes involved in desulfurization (dsz) are located in the chromosome, and PCR amplification was observed with primers dszA and dszB designed based on Rhodococcus genes. However, no amplification product was observed with the primer based on dszC.