{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:22:08Z","timestamp":1790904128675,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,5,28]]},"abstract":"<jats:p>\n                    Purified protein derivative (PPD) skin testing is used to identify persons infected with\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) and to assess cell-mediated immune responses to Mtb. However, lack of skin induration to intradermal injection of PPD or PPD anergy is observed in a subset of patients with active tuberculosis (TB). To investigate the sensitivity and persistence of PPD reactivity and its\n                    <jats:italic>in vitro<\/jats:italic>\n                    correlates during active TB disease and after successful chemotherapy, we evaluated the distribution of skin size induration after intradermal injection of PPD among 364 pulmonary TB patients in Cambodia. A subset of 25 pulmonary TB patients who had a positive skin reaction to mumps and\/or candida antigens showed persistent anergy to PPD after successful completion of TB therapy. Strikingly,\n                    <jats:italic>in vitro<\/jats:italic>\n                    stimulation of T cells from persistently anergic TB patients with mumps but not PPD resulted in T cell proliferation, and lower levels of IL-2 and IFN-\u03b3 and higher levels of IL-10 were detected in PPD-stimulated cellular cultures from PPD-anergic as compared with PPD-reactive pulmonary TB patients. These results show that anergy to PPD is antigen-specific and persistent in a subset of immunocompetent pulmonary TB patients and is characterized by antigen-specific impaired T cell proliferative responses and a distinct pattern of cytokine production including reduced levels of IL-2.\n                  <\/jats:p>","DOI":"10.1073\/pnas.062056099","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:46:49Z","timestamp":1027680409000},"page":"7576-7581","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":86,"title":["Antigen-specific and persistent tuberculin anergy in a cohort of pulmonary tuberculosis patients from rural Cambodia"],"prefix":"10.1073","volume":"99","author":[{"given":"Julio C.","family":"Delgado","sequence":"first","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice Y.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sok","family":"Thim","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Baena","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki A.","family":"Boussiotis","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Reynes","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun","family":"Sath","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Grosjean","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond J.","family":"Yunis","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E.","family":"Goldfeld","sequence":"additional","affiliation":[{"name":"Center for Blood Research, Harvard Medical School, Boston, MA 02115; Departments of Pathology and Medicine, Brigham and Women's Hospital, Boston, MA 02115; Stanford Medical Center, Palo Alto, CA 94303; Cambodian Health Committee and Institut Pasteur du Cambodge, Phnom-Penh, Cambodia; Divisions of Adult Oncology and Cancer Immunology, Dana\u2013Farber Cancer Institute, Boston, MA 02115; and Institut Pasteur de Madagascar, Antananarivo, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,5,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.7.677"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198401000-00003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198612183152502"},{"key":"e_1_3_3_4_2","unstructured":"The World Health Report 2001 (2001) (W.H.O. 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