Impaired B cells survival upon production of inflammatory cytokines by HIV-1 exposed follicular dendritic cells.

BACKGROUND: Follicular dendritic cells (FDCs) are important components in the organization of germinal centers in lymphoid tissue where, following antigen presentation, B cells differentiate into memory B cells. The possibility of establishing primary cell lines from FDCs isolated from lymphoid tissue paved the way for characterization of FDC biological properties. We exposed primary FDC cell lines to HIV-1 strains in vitro and studied changes in the chemo-attractive properties of FDCs and release of inflammatory cytokines. RESULTS: FDC lines expressed several known and putative HIV-1 receptors; viral genome was amplified in HIV-1 exposed FDCs which released low levels of p24 HIV-1 protein in culture supernatants, but were not definitely proven to be productively infected. Exposure of FDCs to HIV-1 strains did not change the expression of markers used to characterize these cells. HIV-1 exposed FDCs, however, changed the expression of chemo-attractants involved in cell recruitment at inflammatory sites and increased the production of several inflammatory cytokines. The inflammatory milieu created upon HIV-1 exposure of FDCs led to impaired B cell survival in vitro and reduced Ig production. CONCLUSIONS: FDC lines exposed to different HIV-1 strains, although not able to support productive HIV-1 replication, show an increased production of inflammatory cytokines. Our in vitro model of interactions between HIV-1 exposed FDC lines and B cells suggest that exposure of FDCs to HIV-1 in vivo can contribute to inflammation within germinal centers and that this pathological event may impair B cell survival and contribute to impaired B cell responses during HIV-1 infection.

Liaison between natural killer cells and dendritic cells in human gestation.

A successful pregnancy relies on immunological adaptations that allow the fetus to grow and develop in the uterus, despite being recognized by maternal immune cells. Among several immunocompetent cell types present within the human maternal/fetal interface, DC-SIGN(+) dendritic cells (DCs) and CD56(+) natural killer (NK) cells are of major importance for early pregnancy maintenance, not only generating maternal immunological tolerance but also regulating stromal cell differentiation. Previous reports show the presence of NK-DC cell conjugates in first trimester human decidua, suggesting that these cells may play a role in the modulation of the local immune response within the uterus. While effective immunity is necessary to protect the mother from harmful pathogens, some form of tolerance must be activated to avoid an immune response against fetal antigens. This review article discusses current evidence concerning the functions of DC and NK cells in pregnancy and their liaison in human decidua.

Dietary nucleotides accelerate changes in intestinal lymphocyte maturation in weanling mice.

OBJECTIVE: Nucleotides, the building blocks of nucleic acids, are normal components of the mammalian diet. These molecules have been implicated in biologic processes, such as the stimulation of the immunologic response. Nucleotides have also been considered as conditionally essential nutrients for infant formulas. The authors evaluated the influence of dietary nucleotides on the expression of several surface antigens by different intestinal lymphocyte populations in weanling mice. METHODS: Mice at weaning were fed a semipurified diet with or without 3 g/kg of each of the following nucleotides: adenosine monophosphate, cytosine monophosphate, guanosine monophosphate, and uridine monophosphate. Animals were killed at different times (0, 4, 7, 12, and 18 days) after weaning, and lymphocytes from intestinal Peyer's patches, epithelium, and lamina propria were isolated. The expression of different antigens (CD3, CD4, CD8alpha, CD8beta, TCRalphabeta, TCRgammadelta, CD5, CD22 and CD45R) was analyzed by flow cytometry. RESULTS: The expression of these antigens changed parallel to the maturation of the lymphocytes from Peyer's patches, epithelium, and lamina propria. However, developmental changes of expression for most of the antigens occurred sooner in the animals fed the diet supplemented with nucleotides. The expression of T and B antigens was different in the lymphocyte populations analyzed and also changed according to the diet within each population. In general, nucleotides promoted the expression of B- and T-helper cell antigens. CONCLUSIONS: The authors conclude that dietary nucleotides may affect the process of maturation and differentiation of intestinal lymphocytes, which usually takes place at weaning.