Altered Fetal Cytokine Profiles Are Associated With Placental Malaria

Oral Abstract We hypothesize that placental malaria causes chronic in utero inflam-mation with compensatory production of IL-10 and induction of Tregs. After birth,cytokine levels normalize, but Tregs may be maintained and downregulate effectiveimmune responses to malaria resulting in increased risk of malaria during infancy.We are currently conductingflow cytometric studies on cord blood to further explorethese hypotheses. Our results might inform the design and implementation of prenatalinterventions to protect the health of pregnant women, newborns and infants from malaria

HIV-Associated Interactions Between Oral Microbiota and Mucosal Immune Cells: Knowledge Gaps and Future Directions

none3openCoker, Modupe O.; Cairo, Cristiana; Garzino-Demo, AlfredoCoker, Modupe O.; Cairo, Cristiana; Garzino-Demo, Alfred

Control of CD56 expression and tumor cell cytotoxicity in human Vγ2Vδ2 T cells

<p>Abstract</p> <p>Background</p> <p>In lymphocyte subsets, expression of CD56 (neural cell adhesion molecule-1) correlates with cytotoxic effector activity. For cells bearing the Vγ2Vδ2 T cell receptor, isoprenoid pyrophosphate stimulation leads to uniform activation and proliferation, but only a fraction of cells express CD56 and display potent cytotoxic activity against tumor cells. Our goal was to show whether CD56 expression was regulated stochastically, similar to conventional activation antigens, or whether CD56 defined a lineage of cells committed to the cytotoxic phenotype.</p> <p>Results</p> <p>Tracking individual cell clones defined by their Vγ2 chain CDR3 region sequences, we found that CD56 was expressed on precursor cytotoxic T cells already present in the population irrespective of their capacity to proliferate after antigen stimulation. Public T cell receptor sequences found in the CD56+ subset from one individual might appear in the CD56- subset of another donor. The commitment of individual clones to CD56+ or CD56- lineages was stable for each donor over a 1 year interval.</p> <p>Conclusion</p> <p>The ability to express CD56 was not predicted by TCR sequence or by the strength of signal received by the TCR. For γδ T cells, cytotoxic effector function is acquired when cytotoxic precursors within the population are stimulated to proliferate and express CD56. Expression of CD56 defines a committed lineage to the cytotoxic phenotype.</p

Gamma Interferon Secretion by Human Vγ2Vδ2 T Cells after Stimulation with Antibody against the T-Cell Receptor plus the Toll-Like Receptor 2 Agonist Pam(3)Cys

Circulating Vγ2Vδ2 T-cell populations in healthy human beings are poised for rapid responses to bacterial or viral pathogens. We asked whether Vγ2Vδ2 T cells use the Toll-like receptor (TLR) family to recognize pathogen-associated molecular pattern molecules and to regulate cell functions. Analysis of expanded Vγ2Vδ2 T-cell lines showed the abundant presence of TLR2 mRNA, implying that these receptors are important for cell differentiation or function. However, multiple efforts to detect TLR2 protein on the cell surface or in cytoplasmic compartments gave inconsistent results. Functional assays confirmed that human Vγ2Vδ2 T cells could respond to the TLR2 agonist (S)-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys(4)-OH trihydrochloride (Pam(3)Cys), but the response required coincident stimulation through the γδ T-cell receptor (TCR). Dually stimulated cells produced higher levels of cytoplasmic or cell-free gamma interferon and showed increased expression of the lysosome-associated membrane protein CD107a on the cell surface. A functional TLR2 that requires coincident TCR stimulation may increase the initial potency of Vγ2Vδ2 T-cell responses at the site of infection and promote the rapid development of subsequent acquired antipathogen immunity