Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3high regulatory T cells in humans.

Abstract

CD4(+) regulatory T (Treg) cells expressing CD25 and the transcription factor forkhead box P3 (FOXP3) are indispensable for immunological self-tolerance and homeostasis. FOXP3(+)CD25(+)CD4(+) T cells in humans, however, are heterogeneous in function and differentiation status, including suppressive or nonsuppressive cells as well as resting or activated Treg cells. We have searched for cell surface markers specific for suppression-competent Treg cells by using a panel of currently available monoclonal antibodies reactive with human T cells. We found that CD15s (sialyl Lewis x) was highly specific for activated, terminally differentiated, and most suppressive FOXP3(high) effector Treg (eTreg) cells and able to differentiate them in various clinical settings from nonsuppressive FOXP3(+) T cells secreting inflammatory cytokines. For example, CD15s(+)FOXP3(+) eTreg cells were increased in sarcoidosis, whereas it was nonsuppressive CD15s(-)FOXP3(+) T cells that were expanded in lupus flares. FOXP3(+) cells induced from conventional CD4(+) T cells by T-cell receptor stimulation hardly expressed CD15s. CD15s(+)CD4(+) T-cell depletion was sufficient to evoke and enhance in vitro immune responses against tumor or viral antigens. Collectively, we have identified CD15s as a biomarker instrumental in both phenotypic and functional analysis of FOXP3(+)CD4(+) T-cell subpopulations in health and disease. It allows specific targeting of eTreg cells, rather than whole FOXP3(+)CD4(+) T cells, in controlling immune responses.

• Authors: Makoto Miyara, Driss Chader, Edouard Sage, Daisuke Sugiyama, Hiroyoshi Nishikawa, Diane Bouvry, Laetitia Claër, Ravi Hingorani, Robert Balderas, Jurg Rohrer, Noel Warner, Alain Chapelier, Dominique Valeyre, Reiji Kannagi, Shimon Sakaguchi, Zahir Amoura, Guy Gorochov
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 112 Issue 23 Pg. 7225-30 (Jun 09 2015) ISSN: 1091-6490 [Electronic] United States
• PMID: 26015572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Cytokines
• FOXP3 protein, human
• Forkhead Transcription Factors
• Inflammation Mediators
• Lewis X Antigen
• Sialyl Lewis X Antigen

Topics

• Antibodies, Monoclonal (immunology)
• Cytokines (metabolism)
• Flow Cytometry
• Forkhead Transcription Factors (immunology)
• Humans
• Inflammation Mediators (metabolism)
• Lewis X Antigen (immunology)
• Sialyl Lewis X Antigen
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Thymus Gland (cytology, immunology)