{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:21:29Z","timestamp":1790925689980,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Exaggerated CD4+ T helper 2\u2013specific cytokine producing memory T cell responses developing concomitantly with a T helper 1 response might have a detrimental role in immunity to infection caused by Mycobacterium tuberculosis. To assess the dynamics of Ag-specific memory T cell compartments in the context of filarial infection, we used multiparameter flow cytometry on PBMCs from 25 microfilaremic filarial-infected (Inf) and 14 filarial-uninfected (Uninf) subjects following stimulation with filarial Ag (BmA) or with the M. tuberculosis\u2013specific Ag culture filtrate protein-10 (CFP-10). Our data demonstrated that the Inf group had a marked increase in BmA-specific CD4+IL-4+ cells (median net frequency compared with baseline [Fo] = 0.09% versus 0.01%; p = 0.038) but also to CFP-10 (Fo = 0.16% versus 0.007%; p = 0.04) and staphylococcal enterotoxin B (Fo = 0.49% versus 0.26%; p = 0.04). The Inf subjects showed a BmA-specific expansion of CD4+CD45RO+IL-4+ producing central memory (TCM, CD45RO+CCR7+CD27+; Fo = 1.1% versus 0.5%; p = 0.04) as well as effector memory (TEM, CD45RO+CCR7\u2212CD27\u2212; Fo = 1.5% versus 0.2%; p = 0.03) with a similar but nonsignificant response to CFP-10. In addition, there was expansion of CD4+IL-4+CD45RA+CCR7+CD27+ (naive-like) in Inf individuals compared with Uninf subjects. Among Inf subjects with definitive latent tuberculosis, there were no differences in frequencies of IL-4\u2013producing cells within any of the memory compartments compared with the Uninf group. Our data suggest that filarial infection induces Ag-specific, exaggerated IL-4 responses in distinct T cell memory compartments to M. tuberculosis\u2013specific Ags, which are attenuated in subjects who are able to mount a delayed type hypersensitivity reaction to M. tuberculosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1402718","type":"journal-article","created":{"date-parts":[[2015,2,10]],"date-time":"2015-02-10T01:09:58Z","timestamp":1423530598000},"page":"2706-2714","source":"Crossref","is-referenced-by-count":22,"title":["Filarial Infection Modulates the Immune Response to\n                    <i>Mycobacterium tuberculosis<\/i>\n                    through Expansion of CD4+ IL-4 Memory T Cells"],"prefix":"10.1093","volume":"194","author":[{"given":"Soumya","family":"Chatterjee","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn E","family":"Clark","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Lugli","sequence":"additional","affiliation":[{"name":"Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Roederer","sequence":"additional","affiliation":[{"name":"Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B","family":"Nutman","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,3,15]]},"reference":[{"key":"2025030705281330400_r1","doi-asserted-by":"crossref","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":"2025030705281330400_r2","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.4049\/jimmunol.1300911","article-title":"IL-4-, TGF-\u03b2-, and IL-1-dependent expansion of parasite antigen-specific Th9 cells is associated with clinical pathology in human lymphatic filariasis","volume":"191","author":"Anuradha","year":"2013","journal-title":"J. Immunol."},{"key":"2025030705281330400_r3","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.4049\/jimmunol.148.10.3264","article-title":"Infection with Schistosoma mansoni alters Th1\/Th2 cytokine responses to a non-parasite antigen","volume":"148","author":"Kullberg","year":"1992","journal-title":"J. Immunol."},{"key":"2025030705281330400_r4","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1128\/IAI.72.5.2598-2604.2004","article-title":"Impairment of tetanus-specific cellular and humoral responses following tetanus vaccination in human lymphatic filariasis","volume":"72","author":"Nookala","year":"2004","journal-title":"Infect. Immun."},{"key":"2025030705281330400_r5","article-title":"Global tuberculosis report 2013","author":"World Health Organization","year":"2013"},{"key":"2025030705281330400_r6","first-page":"56","article-title":"Fifteen year follow up of trial of BCG vaccines in south India for tuberculosis prevention. Tuberculosis Research Centre (ICMR), Chennai","volume":"110","year":"1999","journal-title":"Indian J. Med. Res."},{"key":"2025030705281330400_r7","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/infdis\/164.3.581","article-title":"Immunologic responses to repeated ivermectin treatment in patients with onchocerciasis","volume":"164","author":"Steel","year":"1991","journal-title":"J. Infect. Dis."},{"key":"2025030705281330400_r8","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1046\/j.1365-2249.1999.01015.x","article-title":"Onchocerciasis modulates the immune response to mycobacterial antigens","volume":"117","author":"Stewart","year":"1999","journal-title":"Clin. Exp. Immunol."},{"key":"2025030705281330400_r9","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ymeth.2012.12.012","article-title":"IGRAs\u2014the gateway to T cell based TB diagnosis","volume":"61","author":"Whitworth","year":"2013","journal-title":"Methods"},{"key":"2025030705281330400_r10","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1084\/jem.20070567","article-title":"Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection","volume":"204","author":"Okoye","year":"2007","journal-title":"J. Exp. Med."},{"key":"2025030705281330400_r11","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1365-2249.2008.03610.x","article-title":"Persistent human immunodeficiency virus-1 antigenaemia affects the expression of interleukin-7Ralpha on central and effector memory CD4+ and CD8+ T cell subsets","volume":"152","author":"Mercier","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"2025030705281330400_r12","doi-asserted-by":"crossref","first-page":"e19197","DOI":"10.1371\/journal.pone.0019197","article-title":"Altered T cell memory and effector cell development in chronic lymphatic filarial infection that is independent of persistent parasite antigen","volume":"6","author":"Steel","year":"2011","journal-title":"PLoS ONE"},{"key":"2025030705281330400_r13","volume-title":"Manual of Clinical Microbiology.","author":"McPherson","year":"2007"},{"key":"2025030705281330400_r14","doi-asserted-by":"crossref","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":"2025030705281330400_r15","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1182\/blood-2010-03-275438","article-title":"Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates","volume":"116","author":"Lugli","year":"2010","journal-title":"Blood"},{"key":"2025030705281330400_r16","doi-asserted-by":"crossref","first-page":"A62","DOI":"10.1016\/S0167-5699(05)80018-0","article-title":"Regulation and biological function of helminth-induced cytokine responses","volume":"12","author":"Finkelman","year":"1991","journal-title":"Immunol. Today"},{"key":"2025030705281330400_r17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.0105-2896.2004.00187.x","article-title":"Th2 response polarization during infection with the helminth parasite Schistosoma mansoni","volume":"201","author":"Pearce","year":"2004","journal-title":"Immunol. Rev."},{"key":"2025030705281330400_r18","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.4049\/jimmunol.151.7.3704","article-title":"IL-4- and IL-5-secreting lymphocyte populations are preferentially stimulated by parasite-derived antigens in human tissue invasive nematode infections","volume":"151","author":"Mahanty","year":"1993","journal-title":"J. Immunol."},{"key":"2025030705281330400_r19","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1093\/infdis\/171.3.652","article-title":"Immunity to onchocerciasis: putative immune persons produce a Th1-like response to Onchocerca volvulus","volume":"171","author":"Elson","year":"1995","journal-title":"J. Infect. Dis."},{"key":"2025030705281330400_r20","doi-asserted-by":"crossref","first-page":"4857","DOI":"10.4049\/jimmunol.151.9.4857","article-title":"Modulation of murine cytokine responses to mycobacterial antigens by helminth-induced T helper 2 cell responses","volume":"151","author":"Pearlman","year":"1993","journal-title":"J. Immunol."},{"key":"2025030705281330400_r21","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1128\/IAI.70.3.1475-1480.2002","article-title":"Transmission intensity affects both antigen-specific and nonspecific T-cell proliferative responses in Loa loa infection","volume":"70","author":"Akue","year":"2002","journal-title":"Infect. Immun."},{"key":"2025030705281330400_r22","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/eji.1830260233","article-title":"In Th2-biased lymphatic filarial patients, responses to purified protein derivative of Mycobacterium tuberculosis remain Th1","volume":"26","author":"Sartono","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"2025030705281330400_r23","first-page":"26","article-title":"Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis","volume":"89","author":"Hern\u00e1ndez-Pando","year":"1996","journal-title":"Immunology"},{"key":"2025030705281330400_r24","doi-asserted-by":"crossref","first-page":"6436","DOI":"10.1128\/IAI.70.11.6436-6443.2002","article-title":"Evidence inconsistent with a negative influence of T helper 2 cells on protection afforded by a dominant T helper 1 response against Mycobacterium tuberculosis lung infection in mice","volume":"70","author":"Jung","year":"2002","journal-title":"Infect. Immun."},{"key":"2025030705281330400_r25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/1471-2334-6-105","article-title":"Tuberculosis associated with Mycobacterium tuberculosis Beijing and non-Beijing genotypes: a clinical and immunological comparison","volume":"6","author":"Sun","year":"2006","journal-title":"BMC Infect. Dis."},{"key":"2025030705281330400_r26","doi-asserted-by":"crossref","first-page":"e59461","DOI":"10.1371\/journal.pone.0059461","article-title":"Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum","volume":"8","author":"Nolan","year":"2013","journal-title":"PLoS ONE"},{"key":"2025030705281330400_r27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1046\/j.1365-2613.2000.00152.x","article-title":"Treatment with BB-94, a broad spectrum inhibitor of zinc-dependent metalloproteinases, causes deviation of the cytokine profile towards type-2 in experimental pulmonary tuberculosis in Balb\/c mice","volume":"81","author":"Hernandez-Pando","year":"2000","journal-title":"Int. J. Exp. Pathol."},{"key":"2025030705281330400_r28","first-page":"30","article-title":"DNA vaccines against tuberculosis","volume":"1","author":"Lowrie","year":"1999","journal-title":"Curr. Opin. Mol. Ther."},{"key":"2025030705281330400_r29","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1002\/eji.1830181102","article-title":"Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation","volume":"18","author":"Merkenschlager","year":"1988","journal-title":"Eur. J. Immunol."},{"key":"2025030705281330400_r30","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.4049\/jimmunol.140.7.2171","article-title":"Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells","volume":"140","author":"Akbar","year":"1988","journal-title":"J. Immunol."},{"key":"2025030705281330400_r31","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1002\/eji.201343751","article-title":"The who\u2019s who of T-cell differentiation: human memory T-cell subsets","volume":"43","author":"Mahnke","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"2025030705281330400_r32","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nm917","article-title":"Duration of antiviral immunity after smallpox vaccination","volume":"9","author":"Hammarlund","year":"2003","journal-title":"Nat. Med."},{"key":"2025030705281330400_r33","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/COH.0b013e3283413775","article-title":"Maintenance of CD4+ T-cell memory and HIV persistence: keeping memory, keeping HIV","volume":"6","author":"Chomont","year":"2011","journal-title":"Curr Opin HIV AIDS"},{"key":"2025030705281330400_r34","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: implications for vaccine design","volume":"8","author":"Seder","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025030705281330400_r35","first-page":"347","article-title":"Effector memory T-cells dominate immune responses in tuberculosis treatment: antigen or bacteria persistence?","volume":"14","author":"Tapaninen","year":"2010","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"2025030705281330400_r36","doi-asserted-by":"crossref","first-page":"e36046","DOI":"10.1371\/journal.pone.0036046","article-title":"Distinct effector memory CD4+ T cell signatures in latent Mycobacterium tuberculosis infection, BCG vaccination and clinically resolved tuberculosis","volume":"7","author":"Adekambi","year":"2012","journal-title":"PLoS ONE"},{"key":"2025030705281330400_r37","doi-asserted-by":"crossref","first-page":"7759","DOI":"10.1128\/IAI.73.11.7759-7764.2005","article-title":"Memory T lymphocytes generated by Mycobacterium bovis BCG vaccination reside within a CD4 CD44lo CD62 ligand(hi) population","volume":"73","author":"Kipnis","year":"2005","journal-title":"Infect. Immun."},{"key":"2025030705281330400_r38","first-page":"594","article-title":"Superior T memory stem cell persistence supports long-lived T cell memory","volume":"123","author":"Lugli","year":"2013","journal-title":"J. Clin. Invest."},{"key":"2025030705281330400_r39","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/1074-7613(95)90011-X","article-title":"Developmental commitment to the Th2 lineage by extinction of IL-12 signaling","volume":"2","author":"Szabo","year":"1995","journal-title":"Immunity"},{"key":"2025030705281330400_r40","doi-asserted-by":"crossref","first-page":"9307","DOI":"10.1073\/pnas.0704807105","article-title":"Flexibility accompanies commitment of memory CD4 lymphocytes derived from IL-4 locus-activated precursors","volume":"105","author":"Adeeku","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030705281330400_r41","doi-asserted-by":"crossref","first-page":"5306","DOI":"10.4049\/jimmunol.175.8.5306","article-title":"Systemic dissemination and persistence of Th2 and type 2 cells in response to infection with a strictly enteric nematode parasite","volume":"175","author":"Mohrs","year":"2005","journal-title":"J. Immunol."},{"key":"2025030705281330400_r42","doi-asserted-by":"crossref","first-page":"511","DOI":"10.4049\/jimmunol.177.1.511","article-title":"Persistence and function of central and effector memory CD4+ T cells following infection with a gastrointestinal helminth","volume":"177","author":"Zaph","year":"2006","journal-title":"J. Immunol."},{"key":"2025030705281330400_r43","doi-asserted-by":"crossref","first-page":"290","DOI":"10.4049\/jimmunol.159.1.290","article-title":"Human alveolar T lymphocyte responses to Mycobacterium tuberculosis antigens: role for CD4+ and CD8+ cytotoxic T cells and relative resistance of alveolar macrophages to lysis","volume":"159","author":"Tan","year":"1997","journal-title":"J. Immunol."},{"key":"2025030705281330400_r44","doi-asserted-by":"crossref","first-page":"12423","DOI":"10.1073\/pnas.0806372105","article-title":"In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2 lymphocyte differentiation","volume":"105","author":"van Panhuys","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030705281330400_r45","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1128\/IAI.73.6.3394-3401.2005","article-title":"Transcriptional control of impaired Th1 responses in patent lymphatic filariasis by T-box expressed in T cells and suppressor of cytokine signaling genes","volume":"73","author":"Babu","year":"2005","journal-title":"Infect. Immun."},{"key":"2025030705281330400_r46","doi-asserted-by":"crossref","first-page":"e94603","DOI":"10.1371\/journal.pone.0094603","article-title":"Incidence of active pulmonary tuberculosis in patients with coincident filarial and\/or intestinal helminth infections followed longitudinally in South India","volume":"9","author":"Chatterjee","year":"2014","journal-title":"PLoS ONE"},{"key":"2025030705281330400_r47","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.immuni.2009.12.004","article-title":"Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions","volume":"32","author":"Hegazy","year":"2010","journal-title":"Immunity"},{"key":"2025030705281330400_r48","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.immuni.2008.12.009","article-title":"Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells","volume":"30","author":"Wei","year":"2009","journal-title":"Immunity"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/6\/2706\/62235598\/1402718.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/6\/2706\/62235598\/1402718.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T01:47:43Z","timestamp":1741312063000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/194\/6\/2706\/7960919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,3,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1402718","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,3]]},"published":{"date-parts":[[2015,3]]}}}