{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:15:58Z","timestamp":1785798958141,"version":"3.56.0"},"reference-count":74,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,3]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    This systematic review examines the multifaceted roles of \u03b3\u03b4 T cells in malaria and tuberculosis (TB) with an emphasis on subset-specific dynamics and functional plasticity. In malaria, \u03b3\u03b4 T cells, particularly V\u03b39V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    cells, are rapidly activated upon infection with\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    , exerting antiparasitic effects through the production of proinflammatory cytokines, cytotoxicity, and immune modulation. However, chronic or repeated exposure to malaria leads to the functional exhaustion of V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    cells, which is characterized by reduced cytokine responsiveness and a shift toward regulatory phenotypes. In TB, \u03b3\u03b4 T cells contribute to pathogen containment through the secretion of interferon-\u03b3 and interleukin-17, the activation of macrophages, and the formation of granulomas. Yet, active TB is often associated with reduced peripheral \u03b3\u03b4 T-cell frequencies, possibly because of tissue migration or exhaustion. Emerging evidence also highlights distinct roles for CD8\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells and V\u03b41\n                    <jats:sup>+<\/jats:sup>\n                    subsets in latent infection and local tissue immunity. Understanding the pathogen-specific and context-dependent functions of \u03b3\u03b4 T-cell subsets is critical for informing the development of targeted immunotherapies and vaccine strategies against malaria and TB.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.25-0316","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T15:04:37Z","timestamp":1759849477000},"page":"1178-1184","source":"Crossref","is-referenced-by-count":1,"title":["Exploring \u03b3\u03b4 T-Cell Responses in Malaria and Tuberculosis: Implications for Immunity, Coinfection, and Disease Management"],"prefix":"10.4269","volume":"113","author":[{"given":"Yaquta Nur","family":"Mohamud","sequence":"first","affiliation":[{"name":"Graduate Program in Translational Bioclinical Sciences and Innovation, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanna","family":"Chaijaroenkul","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Bioclinical Sciences and Innovation, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesara","family":"Na-Bangchang","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Bioclinical Sciences and Innovation, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Crit Rev Immunol","first-page":"43","article-title":"\u03b3\u03b4 T cells in skin inflammation","volume":"42","author":"Zhang","year":"2022"},{"key":"b2","series-title":"Signal Transduct Target Ther","first-page":"434","article-title":"\u03b3\u03b4 T cells: Origin and fate, subsets, diseases and immunotherapy","volume":"8","author":"Hu","year":"2023"},{"key":"b3","series-title":"Nat Rev Immunol","first-page":"221","article-title":"\u03b3\u03b4 T cells in tissue physiology and surveillance","volume":"21","author":"Ribot","year":"2021"},{"key":"b4","series-title":"Cell Mol Immunol","first-page":"925","article-title":"Cancer immunotherapy with \u03b3\u03b4 T cells: Many paths ahead of us","volume":"17","author":"Kabelitz","year":"2020"},{"key":"b5","series-title":"Cells","first-page":"1206","article-title":"The role of human \u03b3\u03b4 T cells in anti-tumor immunity and their potential for cancer immunotherapy","volume":"9","author":"Liu","year":"2020"},{"key":"b6","series-title":"Cell Immunol","first-page":"31","article-title":"Human gamma delta T cells: Evolution and ligand recognition","volume":"296","author":"Adams","year":"2015"},{"key":"b7","series-title":"Curr Mol Med","first-page":"437","article-title":"Biology of gammadelta T cells in tuberculosis and malaria","volume":"1","author":"Dieli","year":"2001"},{"key":"b8","series-title":"PLoS One","first-page":"e13588","article-title":"Transmission intensity and drug resistance in malaria population dynamics: Implications for climate change","volume":"5","author":"Artzy-Randrup","year":"2010"},{"key":"b9","series-title":"Oxf Open Immunol","first-page":"iqad008","article-title":"Malaria and tuberculosis co-infection\u2014A review","volume":"4","author":"Bijker","year":"2023"},{"key":"b10","series-title":"FEBS J","first-page":"1118","article-title":"\u03b3\u03b4 T cells in malaria: A double-edged sword","volume":"288","author":"Pamplona","year":"2021"},{"key":"b11","series-title":"J Immunol Res","first-page":"5081634","article-title":"Protective role of \u03b3\u03b4 T cells in different pathogen infections and its potential clinical application","volume":"2018","author":"Zhao","year":"2018"},{"key":"b12","series-title":"PLoS Med","first-page":"e1003583","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"18","author":"Page","year":"2021"},{"key":"b13","series-title":"BMC Res Notes","first-page":"76","article-title":"Haematological parameters, natural regulatory CD4 + CD25 + FOXP3+ T cells and \u03b3\u03b4 T cells among two sympatric ethnic groups having different susceptibility to malaria in Burkina Faso","volume":"5","author":"Sanou","year":"2012"},{"key":"b14","series-title":"J Infect Dis","first-page":"1653","article-title":"Cord blood V\u03b32V\u03b42 T cells provide a molecular marker for the influence of pregnancy-associated malaria on neonatal immunity","volume":"209","author":"Cairo","year":"2014"},{"key":"b15","series-title":"Front Immunol","first-page":"1385380","article-title":"Phenotypic changes of \u03b3\u03b4 T cells in Plasmodium falciparum placental malaria and pregnancy outcomes in women at delivery in Cameroon","volume":"15","author":"Nana","year":"2024"},{"key":"b16","series-title":"Clin Exp Immunol","first-page":"34","article-title":"Lymphocyte activation and subset redistribution in the peripheral blood in acute malaria illness: Distinct gammadelta+ T cell patterns in Plasmodium falciparum and P. vivax infections","volume":"108","author":"Worku","year":"1997"},{"key":"b17","series-title":"Infect Immun","first-page":"3190","article-title":"Perturbation and proinflammatory type activation of V delta 1(+) gamma delta T cells in African children with Plasmodium falciparum malaria","volume":"69","author":"Hviid","year":"2001"},{"key":"b18","series-title":"Infect Immun","first-page":"4359","article-title":"The gamma\/delta T-cell response to Plasmodium falciparum malaria in a population in which malaria is endemic","volume":"64","author":"Hviid","year":"1996"},{"key":"b19","series-title":"Front Immunol","first-page":"807765","article-title":"Evidence for an adult-like type 1-immunity phenotype of V\u03b41, V\u03b42 and V\u03b43 T cells in Ghanaian children with repeated exposure to malaria","volume":"13","author":"Le\u00f3n-Lara","year":"2022"},{"key":"b20","series-title":"PLoS One","first-page":"e2027","article-title":"Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans","volume":"3","author":"Todryk","year":"2008"},{"key":"b21","series-title":"PLoS One","first-page":"e0223410","article-title":"Malawian children with uncomplicated and cerebral malaria have decreased activated V\u03b39V\u03b42 \u03b3\u03b4 T cells which increase in convalescence","volume":"14","author":"Harawa","year":"2019"},{"key":"b22","series-title":"Malar J","first-page":"69","article-title":"Longitudinal analysis of gamma delta T cell subsets during malaria infections in Malian adults","volume":"18","author":"Diallo","year":"2019"},{"key":"b23","series-title":"Sci Transl Med","first-page":"eabe7430","article-title":"Repeated Plasmodium falciparum infection in humans drives the clonal expansion of an adaptive \u03b3\u03b4 T cell repertoire","volume":"13","author":"von Borstel","year":"2021"},{"key":"b24","series-title":"J Immunol","first-page":"180","article-title":"Activation of TCR V\u03b41+ and V\u03b41\u2212V\u03b42\u2212 \u03b3\u03b4 T cells upon controlled infection with Plasmodium falciparum in Tanzanian volunteers","volume":"204","author":"Rutishauser","year":"2020"},{"key":"b25","series-title":"Sci Transl Med","first-page":"251ra117","article-title":"Loss and dysfunction of V\u03b42+ \u03b3\u03b4 T cells are associated with clinical tolerance to malaria","volume":"6","author":"Jagannathan","year":"2014"},{"key":"b26","series-title":"Sci Rep","first-page":"11487","article-title":"V\u03b42+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure","volume":"7","author":"Jagannathan","year":"2017"},{"key":"b27","series-title":"J Infect Dis","first-page":"1483","article-title":"Frequent malaria drives progressive V\u03b42 T-cell loss, dysfunction, and CD16 up-regulation during early childhood","volume":"213","author":"Farrington","year":"2016"},{"key":"b28","series-title":"PLoS One","first-page":"e45971","article-title":"Immunity to malaria in Plasmodium vivax infection: A study in central China","volume":"7","author":"Jangpatarapongsa","year":"2012"},{"key":"b29","series-title":"Parasite Immunol","first-page":"e12594","article-title":"Exposure to Plasmodium vivax is associated with the increased expression of exhaustion markers on \u03b3\u03b4 T lymphocytes","volume":"40","author":"Gogoi","year":"2018"},{"key":"b30","series-title":"Sci Rep","first-page":"8844","article-title":"Longitudinal study of changes in \u03b3\u03b4 T cells and CD4+ T cells upon asymptomatic malaria infection in Indonesian children","volume":"7","author":"de Jong","year":"2017"},{"key":"b31","series-title":"J Allergy Clin Immunol","first-page":"1387","article-title":"Delayed expansion of V delta 2+ and V delta 1+ gamma delta T cells after acute Plasmodium falciparum and Plasmodium vivax malaria","volume":"97","author":"Schwartz","year":"1996"},{"key":"b32","series-title":"J Exp Med","first-page":"311","article-title":"Transient increase in circulating gamma\/delta T cells during Plasmodium vivax malarial paroxysms","volume":"179","author":"Perera","year":"1994"},{"key":"b33","series-title":"Clin Transl Immunology","first-page":"e1072","article-title":"Emerging role of \u03b3\u03b4 T cells in vaccine-mediated protection from infectious diseases","volume":"8","author":"Dantzler","year":"2019"},{"key":"b34","series-title":"Clin Exp Immunol","first-page":"233","article-title":"Immune response to Plasmodium vivax has a potential to reduce malaria severity","volume":"160","author":"Chuangchaiya","year":"2010"},{"key":"b35","series-title":"Immunology","first-page":"412","article-title":"Naive human alpha beta T cells respond to membrane-associated components of malaria-infected erythrocytes by proliferation and production of interferon-gamma","volume":"88","author":"Dick","year":"1996"},{"key":"b36","series-title":"Clin Exp Immunol","first-page":"91","article-title":"Human TcR gamma delta+ lymphocyte response on primary exposure to Plasmodium falciparum.","volume":"95","author":"Roussilhon","year":"1994"},{"key":"b37","series-title":"PLoS One","first-page":"e0174718","article-title":"T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti","volume":"12","author":"Lehmann","year":"2017"},{"key":"b38","series-title":"Infect Immun","first-page":"2945","article-title":"V gamma 9V delta 2 T-cell anergy and complementarity-determining region 3-specific depletion during paroxysm of nonendemic malaria infection","volume":"71","author":"Martini","year":"2003"},{"key":"b39","series-title":"PLoS One","first-page":"e0236375","article-title":"Innate immune responses to malaria-infected erythrocytes in pregnant women: Effects of gravidity, malaria infection, and geographic location","volume":"15","author":"Jabbarzare","year":"2020"},{"key":"b40","series-title":"PLoS Pathog","first-page":"e1008997","article-title":"Opsonized antigen activates V\u03b42+ T cells via CD16\/FC\u03b3RIIIa in individuals with chronic malaria exposure","volume":"16","author":"Farrington","year":"2020"},{"key":"b41","series-title":"Microbes Infect","first-page":"680","article-title":"Memory T cells protect against Plasmodium vivax infection","volume":"8","author":"Jangpatarapongsa","year":"2006"},{"key":"b42","series-title":"Clin Exp Immunol","first-page":"385","article-title":"CD3 expression distinguishes two gammadeltaT cell receptor subsets with different phenotype and effector function in tuberculous pleurisy","volume":"157","author":"Yokobori","year":"2009"},{"key":"b43","series-title":"PLoS One","first-page":"e50923","article-title":"CD4-CD8-\u03b1\u03b2 and \u03b3\u03b4 T cells display inflammatory and regulatory potentials during human tuberculosis","volume":"7","author":"Pinheiro","year":"2012"},{"key":"b44","series-title":"Infect Immun","first-page":"5673","article-title":"Immune responsiveness and lymphokine production in patients with tuberculosis and healthy controls","volume":"62","author":"S\u00e1nchez","year":"1994"},{"key":"b45","series-title":"J Immunol","first-page":"1627","article-title":"Activation and regulation of blood V\u03b42 T cells are amplified by TREM-1+ during active pulmonary tuberculosis","volume":"200","author":"Wu","year":"2018"},{"key":"b46","series-title":"Chest","first-page":"195","article-title":"Increased proportions of peripheral blood gamma delta T cells in patients with pulmonary tuberculosis","volume":"102","author":"Ito","year":"1992"},{"key":"b47","series-title":"Kurume Med J","first-page":"5","article-title":"gamma delta T lymphocytes and their V gamma 9 and V delta 2 receptor expression in peripheral blood mononuclear cells of active tuberculosis patients before and after treatment","volume":"47","author":"Saruwatari","year":"2000"},{"key":"b48","series-title":"Kurume Med J","first-page":"175","article-title":"Role of gamma\/delta T-cells in the peripheral blood of patients with pulmonary tuberculosis","volume":"48","author":"Yoshida","year":"2001"},{"key":"b49","series-title":"Respir Med","first-page":"408","article-title":"The T cell receptor subsets of lymphocytes in bronchoalveolar lavage in patients with active pulmonary tuberculosis","volume":"92","author":"Uh","year":"1998"},{"key":"b50","series-title":"JCI Insight","first-page":"e121899","article-title":"Mucosal-associated invariant and \u03b3\u03b4 T cell subsets respond to initial Mycobacterium tuberculosis infection","volume":"3","author":"Vorkas","year":"2018"},{"key":"b51","series-title":"Am J Trop Med Hyg","first-page":"690","article-title":"Innate and adaptive immune responses during acute M. tuberculosis infection in adult household contacts in Kampala, Uganda","volume":"86","author":"Mahan","year":"2012"},{"key":"b52","series-title":"Thorax","first-page":"357","article-title":"gammadelta T lymphocytes in the peripheral blood of patients with tuberculosis with and without HIV co-infection","volume":"57","author":"Carvalho","year":"2002"},{"key":"b53","series-title":"Cells","first-page":"1529","article-title":"Deep immunoprofiling of large-scale tuberculosis dataset at single cell resolution reveals a CD81bright \u03b3\u03b4 T cell population associated with latency","volume":"13","author":"Shekarkar Azgomi","year":"2024"},{"key":"b54","series-title":"FEMS Immunol Med Microbiol","first-page":"339","article-title":"Gamma delta T cell responses associated with the development of tuberculosis in health care workers","volume":"43","author":"Ordway","year":"2005"},{"key":"b55","series-title":"Blood","first-page":"2269","article-title":"Key implication of CD277\/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human \u03b3\u03b4 T-cell subset","volume":"120","author":"Harly","year":"2012"},{"key":"b56","series-title":"Nat Immunol","first-page":"347","article-title":"\u03b3\u03b4 T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis","volume":"22","author":"Junqueira","year":"2021"},{"key":"b57","series-title":"Front Microbiol","first-page":"1288","article-title":"A unique subset of \u03b3\u03b4 T cells expands and produces IL-10 in patients with naturally acquired immunity against falciparum malaria","volume":"8","author":"Taniguchi","year":"2017"},{"key":"b58","series-title":"Vet Immunol Immunopathol","first-page":"1","article-title":"Failure of antigen-stimulated gammadelta T cells and CD4+ T cells from sensitized cattle to upregulate nitric oxide and mycobactericidal activity of autologous Mycobacterium avium subsp. paratuberculosis-infected macrophages","volume":"116","author":"Simutis","year":"2007"},{"key":"b59","series-title":"Front Immunol","first-page":"2445","article-title":"\u03b3\u03b4 T cells in antimalarial immunity: New insights into their diverse functions in protection and tolerance","volume":"9","author":"Dantzler","year":"2018"},{"key":"b60","series-title":"Front Cell Infect Microbiol","first-page":"1071880","article-title":"Phenotype and function of peripheral blood \u03b3\u03b4 T cells in HIV infection with tuberculosis","volume":"12","author":"Zou","year":"2022"},{"key":"b61","series-title":"Blood","first-page":"1250","article-title":"Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells","volume":"117","author":"Dusseaux","year":"2011"},{"key":"b62","series-title":"PLoS One","first-page":"e17849","article-title":"Regulatory T cell induction during Plasmodium chabaudi infection modifies the clinical course of experimental autoimmune encephalomyelitis","volume":"6","author":"Farias","year":"2011"},{"key":"b63","series-title":"J Immunol","first-page":"1798","article-title":"\u03b3\u03b4 T cells kill Plasmodium falciparum in a granzyme- and granulysin-dependent mechanism during the late blood stage","volume":"204","author":"Hern\u00e1ndez-Casta\u00f1eda","year":"2020"},{"key":"b64","series-title":"Microbes Infect","first-page":"255","article-title":"Effector functions and control of human gammadelta T-cell activation","volume":"1","author":"Kabelitz","year":"1999"},{"key":"b65","series-title":"Clin Diagn Lab Immunol","first-page":"1145","article-title":"Cytokines in the pathogenesis of and protection against malaria","volume":"9","author":"Angulo","year":"2002"},{"key":"b66","series-title":"J Immunol","first-page":"3781","article-title":"\u03b3\u03b4 T cells are required for the induction of sterile immunity during irradiated sporozoite vaccinations","volume":"199","author":"Zaidi","year":"2017"},{"key":"b67","series-title":"Clin Exp Immunol","first-page":"287","article-title":"Gamma\/delta T cell subsets in patients with active Mycobacterium tuberculosis infection and tuberculin anergy","volume":"131","author":"Szereday","year":"2003"},{"key":"b68","series-title":"Microb Pathog","first-page":"107032","article-title":"Application of \u03b3\u03b4 T cells with different memory phenotypes in clinical diagnosis of active pulmonary tuberculosis","volume":"198","author":"Liu","year":"2025"},{"key":"b69","series-title":"Clin Dev Immunol","first-page":"628293","article-title":"Understanding delayed T-cell priming, lung recruitment, and airway luminal T-cell responses in host defense against pulmonary tuberculosis","volume":"2012","author":"Shaler","year":"2012"},{"key":"b70","series-title":"Vet Pathol","first-page":"415","article-title":"Reduced formation of granulomata in gamma(delta) T cell knockout BALB\/c mice inoculated with Mycobacterium avium subsp. paratuberculosis","volume":"37","author":"Tanaka","year":"2000"},{"key":"b71","series-title":"Cancer Immunol Immunother","first-page":"1803","article-title":"Human \u03b3\u03b4 T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK","volume":"72","author":"Wang","year":"2023"},{"key":"b72","series-title":"Curr Opin Immunol","first-page":"353","article-title":"gammadelta T cells: An important source of IL-17","volume":"20","author":"Roark","year":"2008"},{"key":"b73","series-title":"Clin Immunol","first-page":"202","article-title":"Immune regulation of gammadelta T cell responses in mycobacterial infections","volume":"116","author":"Chen","year":"2005"},{"key":"b74","series-title":"Virulence","first-page":"2462092","article-title":"Characterization and anti-tuberculosis effects of \u03b3\u03b4 T cells expanded and activated by Mycobacterium tuberculosis heat-resistant antigen","volume":"16","author":"Guo","year":"2025"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/113\/6\/article-p1178.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/113\/6\/article-p1178.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/113\/6\/article-p1178.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T13:32:35Z","timestamp":1764768755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/113\/6\/article-p1178.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":74,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.25-0316","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,3]]}}}