CD4+ T-cell and monocyte interdependence during discordant xenoimmune responses.

Published

Journal Article

This study was designed to examine our hypothesis that human monocytes provide missing constimulatory signals to host CD4+ cells during interactions with porcine endothelial cells (PECs). PECs were isolated from the aorta. Human CD4+ T cells and monocytes were purified from peripheral blood mononuclear cells (PBMCs). A xenogeneic mixed lymphocyte-PEC reaction (xMLER) was performed to determine the proliferation of PBMCs or CD4+ cells in response to PEC. Monocyte-PEC cocultures with or without CD4+ cells were followed by analysis using fluorescence-activated cell scanning (FACS). We evaluated the CD4+ cells proliferation induced by PEC-conditioned monocytes with or without costimulation blockade. xMLER demonstrated strong lymphocyte proliferation in response to PECs. However, purified CD4+ cells showed reduced proliferative responses to PECs when compared with PBMCs. FACS analysis found that CD14+ monocytes up-regulated CD40 and CD80 expressions in the presence of CD4+ cells. PEC-activated but not resting monocytes induced CD4+-cell proliferation, which was inhibited by anti-CD154, anti-CD80, or anti-CD86 antibodies. In summary, human monocytes exposed to PECs are conditioned to up-regulate costimulatory molecules upon exposure to T cells. PEC-conditioned monocytes induced T-cell proliferation by indirect presentation. Costimulation blockade inhibited T-cell proliferation induced by PEC-conditioned monocytes. Our findings suggested that monocytes play an important role in indirect xenoantigen presentation, providing costimulation to T cells. This interaction can occur distant from the initial site of xenoantigen, but monocytes remaide void of costimulatory signals until their interaction with T cells.

Full Text

Duke Authors

Cited Authors

  • Fang, Y; Liu, Z; Zhu, L; Wang, P; Wang, Y; Xu, H

Published Date

  • October 2008

Published In

Volume / Issue

  • 40 / 8

Start / End Page

  • 2764 - 2768

PubMed ID

  • 18929856

Pubmed Central ID

  • 18929856

Electronic International Standard Serial Number (EISSN)

  • 1873-2623

International Standard Serial Number (ISSN)

  • 0041-1345

Digital Object Identifier (DOI)

  • 10.1016/j.transproceed.2008.07.118

Language

  • eng