{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T08:23:35Z","timestamp":1743063815739},"reference-count":23,"publisher":"American Society for Microbiology","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Lymphatic filariasis is known to be associated with diminished CD4<jats:sup>+<\/jats:sup>Th1 and elevated CD4<jats:sup>+<\/jats:sup>Th2 responses to parasite-specific antigens. The roles of cytokine-expressing CD8<jats:sup>+<\/jats:sup>T cells in immune responses to filarial infections are not well defined. To study the roles of CD8<jats:sup>+<\/jats:sup>T cells expressing type 1, type 2, and type 17 cytokines in filarial infections, we examined the frequencies of these cells in clinically asymptomatic, patently infected (INF) individuals, directly<jats:italic>ex vivo<\/jats:italic>and in response to parasite or nonparasite antigens; these frequencies were compared with the results for individuals with filarial lymphedema (i.e., clinical pathology [CP]) and those without active infection or pathology (i.e., endemic normal [EN]). INF individuals exhibited significant decreases in the frequencies of CD8<jats:sup>+<\/jats:sup>T cells expressing tumor necrosis factor alpha (TNF-\u03b1), gamma interferon (IFN-\u03b3), and interleukin-22 (IL-22) at baseline and\/or in response to filarial antigens, compared with CP and EN individuals. In contrast, the same individuals exhibited significant increases in the frequencies of CD8<jats:sup>+<\/jats:sup>T cells expressing IL-4, IL-5, IL-9, IL-13, and IL-21, compared with CP and\/or EN individuals. Curative treatment resulted in significantly increased frequencies of CD8<jats:sup>+<\/jats:sup>T cells expressing IL-2 and significantly decreased frequencies of CD8<jats:sup>+<\/jats:sup>T cells expressing type 2 cytokines. Finally, the regulation of these responses appears to be independent of IL-10 and transforming growth factor \u03b2 (TGF-\u03b2), since blockade of IL-10 or TGF-\u03b2 signaling did not significantly alter the frequencies of type 1 or type 2 cytokine-expressing CD8<jats:sup>+<\/jats:sup>T cells. Our findings suggest that alterations in the frequencies of cytokine-expressing CD8<jats:sup>+<\/jats:sup>T cells are characteristic features of lymphatic filarial infections.<\/jats:p>","DOI":"10.1128\/cvi.00598-14","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T07:00:24Z","timestamp":1411628424000},"page":"1620-1627","source":"Crossref","is-referenced-by-count":17,"title":["Interleukin-10- and Transforming Growth Factor \u03b2-Independent Regulation of CD8<sup>+<\/sup>T Cells Expressing Type 1 and Type 2 Cytokines in Human Lymphatic Filariasis"],"prefix":"10.1128","volume":"21","author":[{"given":"Rajamanickam","family":"Anuradha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parakkal Jovvian","family":"George","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Kumaran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas B.","family":"Nutman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subash","family":"Babu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2014,9,24]]},"reference":[{"key":"key20180919073751_B1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1046\/j.1365-3024.2001.00399.x","article-title":"Regulation of the immune response in lymphatic filariasis: perspectives on acute and chronic infection with Wuchereria bancrofti in South India","volume":"23","author":"Nutman","year":"2001","journal-title":"Parasite Immunol."},{"key":"key20180919073751_B2","first-page":"1","article-title":"Lymphatic filariasis: the disease and its control: fifth report of the WHO Expert Committee on Filariasis","volume":"821","author":"World Health Organization","year":"1992","journal-title":"World Health Organ. Tech. Rep. Ser."},{"key":"key20180919073751_B3","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/S0140-6736(10)60586-7","article-title":"Lymphatic filariasis and onchocerciasis","volume":"376","author":"Taylor","year":"2010","journal-title":"Lancet"},{"key":"key20180919073751_B4","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1007\/s00281-012-0346-4","article-title":"Immunopathogenesis of lymphatic filarial disease","volume":"34","author":"Babu","year":"2012","journal-title":"Semin. Immunopathol."},{"key":"key20180919073751_B5","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/nri1183","article-title":"Immune regulation by helminth parasites: cellular and molecular mechanisms","volume":"3","author":"Maizels","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"key20180919073751_B6","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1111\/pim.12081","article-title":"Immunology of lymphatic filariasis","volume":"36","author":"Babu","year":"2014","journal-title":"Parasite Immunol."},{"key":"key20180919073751_B7","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1172\/JCI116752","article-title":"Cytokine control of parasite-specific anergy in human lymphatic filariasis: preferential induction of a regulatory T helper type 2 lymphocyte subset","volume":"92","author":"King","year":"1993","journal-title":"J. Clin. Invest."},{"key":"key20180919073751_B8","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1093\/infdis\/158.5.1034","article-title":"Enhanced diagnostic specificity in human filariasis by IgG4 antibody assessment","volume":"158","author":"Lal","year":"1988","journal-title":"J. Infect. Dis."},{"key":"key20180919073751_B9","first-page":"327","article-title":"Infections of Brugia pahangi in conventional and nude (athymic) mice","volume":"37","author":"Suswillo","year":"1980","journal-title":"Acta Trop."},{"key":"key20180919073751_B10","doi-asserted-by":"publisher","first-page":"448","DOI":"10.2307\/3280746","article-title":"Development of Brugia pahangi in normal and nude mice","volume":"66","author":"Vincent","year":"1980","journal-title":"J. Parasitol."},{"key":"key20180919073751_B11","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1084\/jem.173.3.659","article-title":"The immunodeficient scid mouse as a model for human lymphatic filariasis","volume":"173","author":"Nelson","year":"1991","journal-title":"J. Exp. Med."},{"key":"key20180919073751_B12","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1128\/IAI.67.6.3166-3167.1999","article-title":"Immunity in experimental murine filariasis: roles of T and B cells revisited","volume":"67","author":"Babu","year":"1999","journal-title":"Infect. Immun."},{"key":"key20180919073751_B13","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1007\/s00281-012-0346-4","article-title":"Immunopathogenesis of lymphatic filarial disease","volume":"34","author":"Babu","year":"2012","journal-title":"Semin. Immunopathol."},{"key":"key20180919073751_B14","first-page":"77","article-title":"Lymphocyte subpopulations in Bancroftian filariasis: activated (DR+) CD8+ T cells in patients with chronic lymphatic obstruction","volume":"77","author":"Lal","year":"1989","journal-title":"Clin. Exp. Immunol."},{"key":"key20180919073751_B15","first-page":"633","article-title":"Predominant CD8+ infiltrate in limb biopsies of individuals with filarial lymphedema and elephantiasis","volume":"53","author":"Freedman","year":"1995","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"key20180919073751_B16","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.4049\/jimmunol.162.3.1756","article-title":"Biased TCR repertoire in infiltrating lesional T cells in human Bancroftian filariasis","volume":"162","author":"Freedman","year":"1999","journal-title":"J. Immunol."},{"key":"key20180919073751_B17","doi-asserted-by":"publisher","first-page":"5375","DOI":"10.4049\/jimmunol.0904067","article-title":"At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells","volume":"184","author":"Metenou","year":"2010","journal-title":"J. Immunol."},{"key":"key20180919073751_B18","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1128\/CVI.00257-14","article-title":"Interleukin 1 (IL-1)- and IL-23-mediated expansion of filarial antigen-specific Th17 and Th22 cells in filarial lymphedema","volume":"21","author":"Anuradha","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"key20180919073751_B19","doi-asserted-by":"publisher","first-page":"e2658","DOI":"10.1371\/journal.pntd.0002658","article-title":"Parasite-antigen driven expansion of IL-5\u2212 and IL-5+ Th2 human subpopulations in lymphatic filariasis and their differential dependence on IL-10 and TGF\u03b2","volume":"8","author":"Anuradha","year":"2014","journal-title":"PLoS Negl. Trop. Dis."},{"key":"key20180919073751_B20","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1146\/annurev.immunol.15.1.323","article-title":"Nitric oxide and macrophage function","volume":"15","author":"MacMicking","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"key20180919073751_B21","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.imlet.2004.01.014","article-title":"Interleukin-17 augments tumor necrosis factor-\u03b1-induced elaboration of proangiogenic factors from fibroblasts","volume":"93","author":"Numasaki","year":"2004","journal-title":"Immunol. Lett."},{"key":"key20180919073751_B22","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1172\/JCI31487","article-title":"Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases","volume":"117","author":"Wynn","year":"2007","journal-title":"J. Clin. Invest."},{"key":"key20180919073751_B23","doi-asserted-by":"publisher","first-page":"e1002003","DOI":"10.1371\/journal.ppat.1002003","article-title":"Evolution of Th2 immunity: a rapid repair response to tissue destructive pathogens","volume":"7","author":"Allen","year":"2011","journal-title":"PLoS Pathog."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/CVI.00598-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,16]],"date-time":"2023-07-16T19:41:49Z","timestamp":1689536509000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00598-14"}},"subtitle":[],"editor":[{"given":"P. P.","family":"Wilkins","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,9,24]]},"references-count":23,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,11,25]]},"published-print":{"date-parts":[[2014,12]]}},"alternative-id":["10.1128\/CVI.00598-14"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00598-14","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,24]]}}}