Granzyme B CD4 T cells accumulate in the colon during chronic HIV-1 infection.

Chronic HIV-1 infection results in the sustained disruption of gut homeostasis culminating in alterations in microbial communities (dysbiosis) and increased microbial translocation. Major questions remain on how interactions between translocating microbes and gut immune cells impact HIV-1-associated gut pathogenesis. We previously reported that exposure of human gut cells to enteric commensal bacteria upregulated the serine protease and cytotoxic marker Granzyme B (GZB) in CD4 T cells, and GZB expression was further increased in HIV-1-infected CD4 T cells.

Reduced immune-regulatory molecule expression on human colonic memory CD4 T cells in older adults.

Background: The etiology of the low-level chronic inflammatory state associated with aging is likely multifactorial, but a number of animal and human studies have implicated a functional decline of the gastrointestinal immune system as a potential driver. Gut tissue-resident memory T cells play critical roles in mediating protective immunity and in maintaining gut homeostasis, yet few studies have investigated the effect of aging on human gut T cell immunity. To determine if aging impacted CD4 T cell immunity in the human large intestine, we utilized multi-color flow cytometry to measure colonic lamina propria (LP) CD4 T cell frequencies and immune-modulatory marker expression in younger (mean ± SEM: 38 ± 1.

Age-related alterations in human gut CD4 T cell phenotype, T helper cell frequencies, and functional responses to enteric bacteria.

Intestinal lamina propria (LP) CD4 T cells play critical roles in maintaining intestinal homeostasis and in immune responses to enteric microbes, yet little is known regarding whether they contribute to age-associated intestinal immune dysfunction. In this study, we evaluated the direct ex vivo frequency, activation/inhibitory phenotype, death profiles, and in vitro functional responses of human jejunum LP CD4 T cells, including Th1, Th17, and Th22 subsets isolated from younger (<45 years) and older (>65years) persons. Expression of the co-inhibitory molecule CTLA-4 was significantly lower in older CD4 T cells, whereas expression of HLA-DR, CD38, CD57, and PD-1 were not significantly different between groups.

An Anticancer Drug Cocktail of Three Kinase Inhibitors Improved Response to a Dendritic Cell-Based Cancer Vaccine.

Monocyte-derived dendritic cell (moDC)-based cancer therapies intended to elicit antitumor T-cell responses have limited efficacy in most clinical trials. However, potent and sustained antitumor activity in a limited number of patients highlights the therapeutic potential of moDCs. culture conditions used to generate moDCs can be inconsistent, and moDCs generated are less effective than natural DCs.