Global Gene Expression of T Cells Is Differentially Regulated by Peritoneal Dendritic Cell Subsets in an IL-2 Dependent Manner

Abstract

Dendritic cells (DCs) in peripheral tissues may have a unique role to regulate innate and adaptive immune responses to antigens that enter the tissues. Peritoneal cavity is the body compartment surrounding various tissues and organs and housing diverse immune cells. Here, we investigated the specialized features of classical DC (cDC) subsets following the intraperitoneal injection of a model antigen ovalbumin (OVA). Peritoneal cDC1s were superior to cDC2s in activating OVA-specific CD8 T cells, while both cDCs were similar in stimulating OVA-specific CD4 T cells. Each peritoneal cDC subset differentially regulated the homing properties of CD8 T cells. CD8 T cells stimulated by cDC1s displayed a higher level of lung-homing receptor CCR4, whereas those stimulated by cDC2s prominently expressed various homing receptors including gut-homing molecules CCR9 and α4β7. Also, we found that cDC1s played a dominating role over cDC2s in controlling the overall gene expression of CD8 T cells. Soluble factor(s) emanating from CD8 T cells stimulated by peritoneal cDC1s were responsible for mediating this dominance of cDC1s, and we identified IL-2 as a soluble factor regulating the global gene expression of T cells. Collectively, our study indicates that different peritoneal cDC subsets effectively diversify T cell responses by altering the level of cytokines, such as IL-2, in the milieu.

Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen

“…Enriched and labeled 5×10 4 naive T cells and graded doses of purified APCs were co-cultured in 96-well round-bottom tissue culture plates with DMC7 medium supplemented with 57.2 mM 2-mercaptoethanol (Sigma-Aldrich). Proliferated T cells were assessed by flow cytometry at 3 to 5 days after culture (34).…”

Identification of dendritic cell precursor from the CD11c+ cells expressing high levels of MHC class II molecules in the culture of bone marrow with FLT3 ligand

“…Then, specific populations of APCs were isolated with flow cytometric sorter as described above. The enrichment of naive CD8 + OT-1 and CD4 + OT-2 T cells from the splenocytes of OT-1 and OT-2 mice respectively were described previously ( 33 , 34 ). Naive OT-1 and OT-2 T cells were labeled with CFSE or CTV at 37°C for 10 minutes and washed with DPBS.…”

Peritoneal Immunity in Liver Disease

“…In humans, they make up 2-5% of peritoneal leukocytes [6]. Although in mice classical DC seem to predominate in the peritoneum [32], in humans myeloid-derived DC have been identified in peritoneal lavage of patients undergoing laparoscopic surgery [33]. These myeloid-derived DCs were important in response to Gram-positive bacteria and imparted a Th1 profile on T cell responses.…”