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HHLA2 is expressed in humans but not in mice, which is unique within the B7 and CD28 families. HHLA2 protein is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation with LPS and IFN-\u03b3. HHLA2 does not interact with other known members of the CD28 family or the B7 family, but does bind a putative receptor that is constitutively expressed not only on resting and activated CD4 and CD8 T cells but also on antigen-presenting cells. HHLA2 inhibits proliferation of both CD4 and CD8 T cells in the presence of T-cell receptor signaling. In addition, HHLA2 significantly reduces cytokine production by T cells including IFN-\u03b3, TNF-\u03b1, IL-5, IL-10, IL-13, IL-17A, and IL-22. Thus, we have identified a unique B7 pathway that is able to inhibit human CD4 and CD8 T-cell proliferation and cytokine production. This unique human T-cell coinhibitory pathway may afford unique strategies for the treatment of human cancers, autoimmune disorders, infection, and transplant rejection and may help to design better vaccines.<\/jats:p>","DOI":"10.1073\/pnas.1303524110","type":"journal-article","created":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T01:46:29Z","timestamp":1369791989000},"page":"9879-9884","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":181,"title":["HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function"],"prefix":"10.1073","volume":"110","author":[{"given":"Ruihua","family":"Zhao","sequence":"first","affiliation":[{"name":"Departments of aMicrobiology and Immunology and"},{"name":"School of Life Science, Fudan University, Shanghai 200433, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M.","family":"Chinai","sequence":"additional","affiliation":[{"name":"Departments of aMicrobiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Buhl","sequence":"additional","affiliation":[{"name":"Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Scandiuzzi","sequence":"additional","affiliation":[{"name":"Departments of aMicrobiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjana","family":"Ray","sequence":"additional","affiliation":[{"name":"Departments of aMicrobiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyungjun","family":"Jeon","sequence":"additional","affiliation":[{"name":"Departments of aMicrobiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim C.","family":"Ohaegbulam","sequence":"additional","affiliation":[{"name":"Departments of aMicrobiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaya","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Departments of aMicrobiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, People\u2019s Republic of China; 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