Transplantation

Oral Abstract Session

Distinct alloimmune stimulatory profile of monocyte-derived dendritic cells and CD40L-stimulated B cells

Friday, June 16
4:00 PM - 4:15 PM

Donor-derived allogeneic B cells have been used to measure alloimmune responses in transplant patients, and to expand alloantigen-reactive regulatory T cells (Tregs) that are being tested clinically to induce tolerance and control rejection in liver and kidney transplant patients. However, dendritic cells (DCs) are potent antigen-presenting cells (APCs) that also contribute to alloimmune responses. Therefore, we compared the T cell-stimulating capacity of human mature monocyte-derived DCs (mDCs), differentiated from CD14+ blood monocytes, to CD40L-stimulated B cells (sBcs). In mixed PBMC and purified T cell cultures, mDCs promoted more robust proliferation of allogeneic Tregs, conventional CD4+ T cells (Tconv), and CD8+ T cells compared to sBcs, correlating with mDCs expressing higher levels of HLA and costimulatory molecules compared to sBcs. Both mDCs and sBcs produced large amounts of the chemokines CCL22 and CCL5, whereas sBcs also produced a high amount of CXCL10. Neither APC type produced much TNFα, IL-1α, IL-1β, IL-6, IL-12p70, or IL-23 that can destabilize Tregs. Additionally, mDCs, but not sBcs, produced IL-1R antagonist. TCR sequencing analysis showed that TCR repertoires of sBc- and mDC-expanded Tregs were diverse. The two repertoires had less than 20% overlap, suggesting the two APC types may stimulate distinct repertoires of alloantigen-reactive T cells. Additional experiments are ongoing to determine repertoires of mDC- and sBc-stimulated Tconv and CD8+ T cells and their relatedness to graft-infiltrating T cells in kidney rejection biopsies. These results will provide important information on which APC type provides more accurate recall of pathogenic and tolerogenic alloimmune responses in transplant patients.

Linda M. Lee

Postdoctoral Scholar
University of California San Francisco

Presentation(s):

Send Email for Linda Lee

Hong Zhang

Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh

Presentation(s):

Send Email for Hong Zhang

Karim Lee

University of California, San Francisco

Presentation(s):

Send Email for Karim Lee

Angus W. Thomson

Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh

Presentation(s):

Send Email for Angus W. Thomson

Qizhi Tang

Director, Transplantation Research Laboratory
UCSF

Presentation(s):

Send Email for Qizhi Tang


Assets

Distinct alloimmune stimulatory profile of monocyte-derived dendritic cells and CD40L-stimulated B cells



Attendees who have favorited this

Send Email for Distinct alloimmune stimulatory profile of monocyte-derived dendritic cells and CD40L-stimulated B cells