Allogeneic dendritic cells stimulated with antibodies against HLA class II polarize naive T cells in a follicular helper phenotype

作者：Desy Olivier; Beland Stephanie; Vallin Patrice; Riopel Julie; Latulippe Eva; Wagner Eric; De Serres Sacha A^*

来源：Scientific Reports, 2018, 8(1): 4025.

DOI：10.1038/s41598-018-22391-w

Follicular helper T cells ( Tfh) are crucial for the production of high-affinity antibodies, such as alloantibodies, by providing the signals for B-cell proliferation and differentiation. Here, we demonstrate that human allogeneic dendritic cells ( DC) stimulated with antibodies against HLA class II antigens preferentially differentiate human naive CD4(+) T cells into Tfh cells. Following coculture with DCs treated with these antibodies, CD4(+) T cells expressed CXCR5, ICOS, IL-21, Bcl-6 and phosphorylated STAT3. Blockade of IL-21 abrogated Bcl-6, while addition of the IL-12p40 subunit to the coculture increased CXCR5, Bcl-6, phosphorylated STAT3 and ICOS, indicating that they were both involved in Tfh polarization. We further phenotyped the peripheral T cells in a cohort of 55 kidney transplant recipients. Patients with anti-HLA-II donor-specific antibodies ( DSA) presented higher blood counts of circulating Tfh cells than those with anti-HLA-I DSAs. Moreover, there was a predominance of lymphoid aggregates containing Tfh cells in biopsies from patients with antibody-mediated rejection and anti-HLA-II DSAs. Collectively, these data suggest that alloantibodies against HLA class II specifically promote the differentiation of naive T cells to Tfh cells following contact with DCs, a process that might appear in situ in human allografts and constitutes a therapeutic target.

• 出版日期2018-3-5