CTLA4 is expressed on mature dendritic cells derived from human monocytes and influences their maturation and antigen presentation

Abstract

BackgroundDendritic cells (DCs) initiate immune responses through their direct interaction with effector cells. However, the mechanism by which DC activity is regulated is not well defined. Previous studies have shown that CTLA4 on T cells regulates DCs function by "cross-talk". We investigated whether there is an intrinsic regulatory mechanism in DCs, with CTLA4 as a candidate regulator.ResultsWe confirmed via RT-PCR and flow cytometry the natural expression of CTLA4 on mature DCs derived from human monocytes. Approximately 8% CD1a-positive cells express CTLA4 both on surface and intracellular, whereas 10% CD1a-negative cells express CTLA4 intracellularly, but little expression was observed on the cell surface. The cross-linking of CTLA4 inhibits DCs maturation and antigen presentation in vitro, but does not inhibit endocytosis.ConclusionsCTLA4 is expressed by DCs and plays an inhibitory role. CTLA4-expressing DCs may represent a group of regulatory DCs. Because of its wide distribution on different cell types, CTLA4 may play a general role in regulating immune responses.

Dendritic Cell-Secreted Cytotoxic T-Lymphocyte-Associated Protein-4 Regulates the T-cell Response by Downmodulating Bystander Surface B7

“…In contrast to the well-known data suggesting lymphoid specificity, there also exist a number of inconclusive reports suggesting expression of CTLA-4 in myeloid lineage hematopoietic cells, including dendritic cells (DC) [23][24][25][26][27]. These sporadic data include a previous report of CTLA-4 mRNA expression from highly purified in vitro-derived myeloid DC [27].…”

“…Although a few sporadic reports previously hinted at myeloid lineage (i.e., DC) CTLA-4 expression, in normal immune homeostasis such reports were rare and largely inconclusive [24][25][26]. In this study, we present for the first time a thorough and conclusive characterization of DC CTLA-4 expression and function.…”

“…Previous sporadic reports have suggested expression of CTLA-4 by DC or CD14 + myeloid cells under a variety of different conditions; however, conclusive characterization this phenomenon has been elusive [23][24][25][26][27]. Given that DC CTLA-4 surface expression is not detectable, we sought to test the hypotheses that DC expression of CTLA-4 could be intracellular, secretory, or a combination of both possibilities.…”

Characterization and functionality of the CD200–CD200R system during mesenchymal stromal cell interactions with T-lymphocytes

“…These data are consistent with many studies reporting the ability of several immune cells to express both CD200R and CD200. Currently, the significance of co-expression of both receptor and ligand within the same cell population is unknown [50][51][52][53]. Because we found that the expression profiles of CD200 and CD200R on MSCs and T-lymphocytes were totally different, we then investigated the importance of the CD200-CD200R interaction in the inhibitory effects of MSCs.…”

Ipilimumab Treatment Results in an Early Decrease in the Frequency of Circulating Granulocytic Myeloid-Derived Suppressor Cells as well as Their Arginase1 Production

“…In addition to being expressed on T cells upon activation, CTLA-4 has been described to be expressed on activated B cells (18), monocytes (19), dendritic cells (20), and activated granulocytes (21). Although expression levels are lower than in T cells, CTLA-4 blockade in these cellular populations may be related to the in trans effects of ipilimumab treatment.…”