The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro.

Abstract

SummaryB7-2 is a recently discovered, second ligand for the CTLA-4/CD28, T cell signaling system. Using the GL-1 rat monoclonal antibody (mAb), we monitored expression of B7-2 on mouse leukocytes with an emphasis on dendritic cells. By cytofluorography, little or no B7-2 was detected on most cell types isolated from spleen, thymus, peritoneal cavity, skin, marrow, and blood. However, expression of B7-2 could be upregulated in culture. In the case of epidermal and spleen dendritic cells, which become highly immunostimulatory for T cells during a short period of culture, the upregulation of B7-2 was dramatic and did not require added stimuli. Lipopolysaccharide did not upregulate B7-2 levels on dendritic cells, in contrast to macrophages and B cells. By indirect immunolabeling, the level of staining with GL-1 mAb exceeded that seen with rat mAbs to several other surface molecules including intercellular adhesion molecule 1, B7-1, CD44, and CD45, as well as new hamster mAbs to CD40, CD48, and B7-1/CD80. Of these accessory molecules, B7-2 was a major species that increased in culture, implying a key role for B7-2 in the functional maturation of dendritic cells. B7-2 was the main (>90%) CTLA-4 ligand on mouse dendritic cells. When we applied GL-1 to tissue sections of a dozen different organs, clear-cut staining with B7-2 antigen was found in many. B7-2 staining was noted on liver Kupffer cells, interstitial cells of heart and lung, and profiles in the submucosa of the esophagus. B7-2 staining was minimal in the kidney and in the nonlymphoid regions of the gut, and was not observed at all in the brain. In the tongue, only rare dendritic cells in the oral epithelium were B7-2 + , but reactive cells were scattered about the interstitial spaces of the muscle. In all lymphoid tissues, GI-1 strongly stained certain distinct regions that are occupied by dendritic cells and by macrophages. For dendritic cells, these include the thvmic medulla, splenic periarterial sheaths, and lymph node deep cortex; for macrophages, the B7-2-rich regions included the splenic marginal zone and lymph node subcapsular cortex. Splenic B7-2 + cells were accessible to labeling with GL-1 mAb given intravenously. Dendritic cell stimulation of T cells (DNA synthesis) during the mixed leukocyte reaction was significantly (35-65%) blocked by GL-1. The block could be enhanced by adding 1G10 anti-B7-1 or by using CTLA-4 Ig, a ligand for both B7-1 and B7-2. We conclude that B7-2, like other accessory molecules, is expressed by many types of antigen-presenting cells. However, the regulation and extent of B7-2 expression seems to differ among cell types. Dendritic cells express very high levels, in several sites in vivo and after maturation into strong accessory cells in culture. CD28 and CTLA-4 are closely related molecules (1, 2) that are expressed on most T cells. CD28 was first identified using monoclonals that were comparably mitogenic to anti-TCR mAbs, when administered together with PMA (3-5). The simultaneous triggering of CD28/CTLA-4 and CD3/TCR,...

In situexpression of B7 and CD40 costimulatory molecules by normal human lung macrophages and epithelioid cells in tuberculoid granulomas

“…Although the expression of B7 molecules has been extensively studied on B cells, less is known concerning their expression by other APC, including monocyte/macrophages. Murine macrophages from several lymphoid and non-lymphoid organs have been shown to poorly express B7 molecules, although expression can be upregulated in vitro by LPS or by interferon-gamma (IFN-g) [19,20]. In humans, resting monocytes constitutively express B7-2, whereas B7-1 expression is inducible in culture, particularly in the presence of IFN-g [21,22].…”

IL-4 Suppresses Dendritic Cell Response to Type I Interferons

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Cloning and characterization of the human CD200 promoter region

“…It should be realized that this ignores (at lem temporarily), for ease of discussion, the potential role for exogenous cytokines in ce11 activation, beyond their role in regdating expression of costimulator molecules (56,57) For further simplification, fkom the perspective of the ligands expressed on APC, the "key" playen in regdating sthuiation are conddered to be members of the CD80ICD86 family, CD40…”