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The Ig superfamily protein glycoprotein A33 (GPA33) has been implicated in immune dysregulation, but little is known about its expression in the immune compartment. Here, we comprehensively determined GPA33 expression patterns on human blood leukocyte subsets, using mass and flow cytometry. We found that GPA33 was expressed on fractions of B, dendritic, natural killer and innate lymphoid cells. Most prominent expression was found in the CD4+ T cell compartment. Naïve and CXCR5+ regulatory T cells were GPA33high, and naïve conventional CD4+ T cells expressed intermediate GPA33 levels. The expression pattern of GPA33 identified functional heterogeneity within the CD4+ central memory T cell (Tcm) population. GPA33+ CD4+ Tcm cells were fully undifferentiated, bona fide Tcm cells that lack immediate effector function, whereas GPA33– Tcm cells exhibited rapid effector functions and may represent an early stage of differentiation into effector/effector memory T cells before loss of CD62L. Expression of GPA33 in conventional CD4+ T cells suggests a role in localization and/or preservation of an undifferentiated state. These results form a basis to study the function of GPA33 and show it to be a useful marker to discriminate between different cellular subsets, especially in the CD4+ T cell lineage. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a T-cell-mediated autoimmune disease in which autoreactive CD8+ T cells destroy the insulin-producing pancreatic beta cells. Vitamin D3 and dexamethasone-modulated dendritic cells ( Combi- DCs) loaded with islet antigens inducing islet-specific regulatory CD4+ T cells may offer a tissue-specific intervention therapy. The effect of Combi- DCs on CD8+ T cells, however, remains unknown. To investigate the interaction of CD8+ T cells with Combi- DCs presenting epitopes on HLA class I, naive, and memory CD8+ T cells were co-cultured with DCs and proliferation and function of peptide-specific T cells were analyzed. Antigen-loaded Combi- DCs were unable to prime naïve CD8+ T cells to proliferate, although a proportion of T cells converted to a memory phenotype. Moreover, expansion of CD8+ T cells that had been primed by mature monocyte-derived DCs (mo DCs) was curtailed by Combi- DCs in co-cultures. Combi- DCs expanded memory T cells once, but CD8+ T-cell numbers collapsed by subsequent re-stimulation with Combi- DCs. Our data point that (re)activation of CD8+ T cells by antigen-pulsed Combi- DCs does not promote, but rather deteriorates, CD8+ T-cell immunity. Yet, Combi- DCs pulsed with CD8+ T-cell epitopes also act as targets of cytotoxicity, which is undesirable for survival of Combi- DCs infused into patients in therapeutic immune intervention strategies. [ABSTRACT FROM AUTHOR]