{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:32:36Z","timestamp":1791282756365,"version":"4.1.0"},"reference-count":52,"publisher":"American Society of Hematology","issue":"9","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human immunodeficiency virus (HIV) infection is characterized by the massive infiltration of secondary lymphoid organs with activated CD8+ T lymphocytes. While converging data indicated that these cells were HIV-specific cytotoxic T lymphocytes (CTLs) responsible for HIV spread limitation, direct evidence was lacking. Here, the presence of HIV-specific effector CTLs was demonstrated directly ex vivo in 15 of 24 microdissected splenic white pulps from an untreated patient and in 1 of 24 tonsil germinal centers from a second patient with incomplete viral suppression following bitherapy. These patients had plasma HIV RNA loads of 5900 and 820 copies per milliliter. The frequencies of HIV-1 DNA+ cells in their lymphoid organs were more than 1 in 50 and 1 in 175, respectively. Spliced viral messenger RNA (a marker for ongoing viral replication) was present in most immunocompetent structures tested. Conversely, CTL activity was not found in spleens from 2 patients under highly active antiretroviral therapy, with undetectable plasma viral load. These patients had much lower spleen DNA+ cell frequencies (1 in 2700 and 1 in 3800) and no white pulps containing spliced RNA. CTL effector activity as well as spliced viral messenger RNA were both concentrated in the white pulps and germinal centers. This colocalization indicates that viral replication in immunocompetent structures of secondary lymphoid organs triggers anti-HIV effector CTLs to these particular locations, providing clues to target therapeutic intervention.<\/jats:p>","DOI":"10.1182\/blood.v97.9.2695","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"2695-2701","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":36,"title":["HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients"],"prefix":"10.1182","volume":"97","author":[{"given":"Anne","family":"Hosmalin","sequence":"first","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assia","family":"Samri","sequence":"additional","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jeanne","family":"Dumaurier","sequence":"additional","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Dudoit","sequence":"additional","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Oksenhendler","sequence":"additional","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Karmochkine","sequence":"additional","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Autran","sequence":"additional","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Wain-Hobson","sequence":"additional","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Re\u0301mi","family":"Cheynier","sequence":"additional","affiliation":[{"name":"From Unite\u0301 INSERM 445, Institut Cochin de Ge\u0301ne\u0301tique Mole\u0301culaire; Laboratoire d'Immunologie Cellulaire et Tissulaire, Ho\u0302pital de la Pitie\u0301-Salpe\u0302trie\u0300re; Unite\u0301 de Re\u0301trovirologie Mole\u0301culaire, Institut Pasteur; Service d'Immuno-He\u0301matologie, Ho\u0302pital St Louis; and Service d'Immunologie Clinique, Ho\u0302pital Europe\u0301en Georges Pompidou; all of Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021217582767300_B1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nm0498-421","article-title":"Antigenic stimulation by BCG vaccine as an in vivo driving force for SIV replication and dissemination.","volume":"4","author":"Cheynier","year":"1998","journal-title":"Nat Med."},{"key":"2020021217582767300_B2","doi-asserted-by":"crossref","first-page":"7772","DOI":"10.1128\/JVI.72.10.7772-7784.1998","article-title":"Effect of immune activation on the dynamics of human immunodeficiency virus replication and on the distribution of viral quasispecies.","volume":"72","author":"Ostrowski","year":"1998","journal-title":"J Virol."},{"key":"2020021217582767300_B3","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S0140-6736(84)90540-3","article-title":"Follicular dendritic cells and virus-like particles in AIDS-related 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antiretroviral triple therapy.","volume":"178","author":"Dalod","year":"1998","journal-title":"J Infect Dis."},{"key":"2020021217582767300_B48","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1097\/00002030-199906180-00011","article-title":"T cell changes after combined nucleoside analogue therapy in HIV primary infection.","volume":"13","author":"Carcelain","year":"1999","journal-title":"AIDS."},{"key":"2020021217582767300_B49","doi-asserted-by":"crossref","first-page":"6721","DOI":"10.1128\/JVI.73.8.6721-6728.1999","article-title":"Levels of HIV-1-specific cytotoxic T-lymphocyte effector and memory responses decline after suppression of viremia wih highly active antiretroviral therapy.","volume":"73","author":"Kalams","year":"1999","journal-title":"J Virol."},{"key":"2020021217582767300_B50","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1097\/00002030-199912030-00008","article-title":"Activation of CD8 T cells normalizes and correlates with the level of provirus in tonsils during highly active antiretroviral therapy in early HIV-1 infection.","volume":"13","author":"Dyrhol-Riise","year":"1999","journal-title":"AIDS."},{"key":"2020021217582767300_B51","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1128\/JVI.72.4.3472-3474.1998","article-title":"Persistent antibody responses but declining CTL responses to multiple HIV type 1 antigens in a long term non progressing individual with a defective p17 proviral sequence and no detectable viral RNA expression.","volume":"72","author":"Binley","year":"1998","journal-title":"J 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