{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T21:26:49Z","timestamp":1769549209377,"version":"3.49.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>During chronic viral infections, T cells are exhausted due to constant antigen exposure and are associated with enhanced programmed death 1 (PD-1) expression. Deficiencies in the PD-1\/programmed death-ligand 1 (PD-L1) pathway are associated with autoimmune diseases, including those of the central nervous system (CNS). To understand the role of PD-1 expression in regulating T-cell immunity in the CNS during chronic infection, we characterized PD-1 expression in cerebrospinal fluid (CSF) and blood of individuals with chronic human immunodeficiency virus type 1 (HIV-1) infection. PD-1 expression was higher on HIV-specific CD8<jats:sup>+<\/jats:sup>T cells than on total CD8<jats:sup>+<\/jats:sup>T cells in both CSF and blood. PD-1 expression on CSF T cells correlated positively with CSF HIV-1 RNA and inversely with blood CD4<jats:sup>+<\/jats:sup>T-cell counts, suggesting that HIV-1 infection drives higher PD-1 expression on CSF T cells. However, in every HIV-positive individual, PD-1 expression was higher on T cells in CSF than on those in blood, despite HIV-1 RNA levels being lower. Among healthy HIV-negative controls, PD-1 expression was higher in CSF than in blood. Furthermore, frequencies of the senescence marker CD57 were lower on CSF T cells than on blood T cells, consistent with our prior observation of enhanced ex vivo functional capacity of CSF T cells. The higher PD-1 expression level on CSF T cells therefore does not reflect cellular exhaustion but may be a mechanism to downregulate immune-mediated tissue damage in the CNS. As inhibition of the PD-1\/PD-L1 pathway is pursued as a therapeutic option for viral infections, potential effects of such a blockade on development of autoimmune responses in the CNS should be considered.<\/jats:p>","DOI":"10.1128\/jvi.01181-09","type":"journal-article","created":{"date-parts":[[2009,10,15]],"date-time":"2009-10-15T01:31:28Z","timestamp":1255570288000},"page":"131-140","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Enhanced PD-1 Expression by T Cells in Cerebrospinal Fluid Does Not Reflect Functional Exhaustion during Chronic Human Immunodeficiency Virus Type 1 Infection"],"prefix":"10.1128","volume":"84","author":[{"given":"Shanmugalakshmi","family":"Sadagopal","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelly L.","family":"Lorey","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Barnett","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Basham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Husamettin","family":"Erdem","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spyros A.","family":"Kalams","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"},{"name":"Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"},{"name":"Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022125"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00373-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-2103"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000179661"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.9.1736"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05115"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.3.1979"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.10.6798"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061800"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5453.602"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00409-07"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)92485-2"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1105"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.08.021"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70230-1"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.4.1888"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737857"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.4049\/jimmunol.149.9.3113","volume":"149","year":"1992","unstructured":"Jassoy, C., R. P. Johnson, B. A. Navia, J. Worth, and B. D. Walker. 1992. Detection of a vigorous HIV-1-specific cytotoxic T lymphocyte response in cerebrospinal fluid from infected persons with AIDS dementia complex. J. Immunol.149:3113-3119.","journal-title":"J. Immunol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21058"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090331"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.04.012"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280490505382"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.10.6738"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20514"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.8.5145"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4794-04.2005"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.9.5812"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.9.5429"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.3.1475-1480.1996"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000155036.03004.a0"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80089-8"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200738071"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00262-4"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061496"},{"key":"e_1_3_2_37_2","first-page":"280","volume":"6","year":"2005","unstructured":"Probst, H. C., K. McCoy, T. Okazaki, T. Honjo, and M. van den Broek. 2005. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat. Immunol.6:280-286.","journal-title":"Nat. Immunol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02021-06"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.38.1.9"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4504-05.2006"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01190-08"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022119"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282eee548"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1443"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410340210"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.3.1333"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1482"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07662"},{"key":"e_1_3_2_49_2","first-page":"250","volume":"21","year":"2007","unstructured":"von Geldern, G., S. Cepok, T. Nolting, Y. Du, V. Grummel, O. Adams, H. P. Hartung, G. Arendt, and B. Hemmer. 2007. CD8 T-cell subsets and viral load in the cerebrospinal fluid of therapy-naive HIV-infected individuals. AIDS21:250-253.","journal-title":"AIDS"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22953"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.25.112701.142822"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01181-09","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01181-09","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T05:14:38Z","timestamp":1685164478000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01181-09"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,1]]}},"alternative-id":["10.1128\/JVI.01181-09"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01181-09","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,1]]},"assertion":[{"value":"2009-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-10-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}