Circulating T follicular helper cells with increased function during chronic graft-versus-host disease

Edouard Forcade, Haesook T. Kim, Corey Cutler, Kathy Wang, Ana C. Alho, Sarah Nikiforow, Vincent T. Ho, John Koreth, Philippe Armand, Edwin P. Alyea, Bruce R. Blazar, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Chronic graft-versus-host disease (cGVHD) remains a major late complication of allogeneic hematopoietic stem cell transplantation (HSCT). Previous studies have established that both donor B and T cells contribute to immune pathology in cGVHD but the mechanisms responsible for coordinated B- and T-cell responses directed against recipient antigens have not been understood. T follicular helper cells (TFH) play an important role in the regulation of B-cell immunity. We performed extensive phenotypic and functional analysis of circulating TFH (cTFH) and B cells in 66 patients after HSCT. Patients with active cGVHD had a significantly lower frequency of cTFH compared with patients without cGVHD. This was associated with higher CXCL13 plasma levels suggesting increased homing of TFH to secondary lymphoid organs. In patients with active cGVHD, cTFH phenotype was skewed toward a highly activated profile with predominance of T helper 2 (Th2)/Th17 subsets. Activated cTFH in patients with cGVHD demonstrated increased functional ability to promote B-cell immunoglobulin secretion and maturation. Moreover, the activation signature of cTFH was highly correlated with increased B-cell activation and plasmablast maturation in patients after transplant. These studies provide new insights into the immune pathogenesis of human cGVHD and identify TFH as a key coordinating element supporting B-cell involvement in this disease.

Original languageEnglish (US)
Pages (from-to)2489-2497
Number of pages9
Issue number20
StatePublished - May 19 2016

Bibliographical note

Funding Information:
The authors thank Kristen Cowens, Steven Paula, Suzan Lazo- Kallanian, and John Daley for excellent assistance with flow cytometry studies and cell sorting, Lauren Gaffny and Doreen Hearsey for their support in obtaining human samples, and M. Fleming and H. Kozakewich for providing human tonsil specimens. This work was supported by National Institutes of Health, National Cancer Institute grants P01CA142106, CA183559, CA183560, Leukemia and Lymphoma Translational Research Grant 6462-15, and the MD-PhD Program (Bordeaux Teaching Hospital, France).

Publisher Copyright:
© 2016 by The American Society of Hematology.


Dive into the research topics of 'Circulating T follicular helper cells with increased function during chronic graft-versus-host disease'. Together they form a unique fingerprint.

Cite this