{"entity": "researcher", "timestamp": "2026-08-22T07:49:02.708Z", "family": "Gaballa", "given": "Ahmed", "initials": "A", "orcid": "0000-0002-5277-5129", "affiliations": ["Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. ahmed.gaballa@ki.se."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/b062c2e7638440919938a93892cf7848.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/b062c2e7638440919938a93892cf7848"}}, "publications": [{"entity": "publication", "iuid": "f1651733b59a4c768b41daa20f04d951", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f1651733b59a4c768b41daa20f04d951.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f1651733b59a4c768b41daa20f04d951"}}, "title": "Revisiting the Role of \u03b3\u03b4 T Cells in Anti-CMV Immune Response after Transplantation.", "authors": [{"family": "Gaballa", "given": "Ahmed", "initials": "A", "orcid": "0000-0002-5277-5129", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b062c2e7638440919938a93892cf7848.json"}}, {"family": "Alagrafi", "given": "Faisal", "initials": "F"}, {"family": "Uhlin", "given": "Michael", "initials": "M", "orcid": "0000-0002-2177-6727", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/116cfe482bb941159ee2e7175f1cd095.json"}}, {"family": "Stikvoort", "given": "Arwen", "initials": "A"}], "type": "journal article", "published": "2021-05-29", "journal": {"title": "Viruses", "issn": "1999-4915", "volume": "13", "issue": "6", "issn-l": "1999-4915"}, "abstract": "Gamma delta (\u03b3\u03b4) T cells form an unconventional subset of T lymphocytes that express a T cell receptor (TCR) consisting of \u03b3 and \u03b4 chains. Unlike conventional \u03b1\u03b2 T cells, \u03b3\u03b4 T cells share the immune signature of both the innate and the adaptive immunity. These features allow \u03b3\u03b4 T cells to act in front-line defense against infections and tumors, rendering them an attractive target for immunotherapy. The role of \u03b3\u03b4 T cells in the immune response to cytomegalovirus (CMV) has been the focus of intense research for several years, particularly in the context of transplantation, as CMV reactivation remains a major cause of transplant-related morbidity and mortality. Therefore, a better understanding of the mechanisms that underlie CMV immune responses could enable the design of novel \u03b3\u03b4 T cell-based therapeutic approaches. In this regard, the advent of next-generation sequencing (NGS) and single-cell TCR sequencing have allowed in-depth characterization of CMV-induced TCR repertoire changes. In this review, we try to shed light on recent findings addressing the adaptive role of \u03b3\u03b4 T cells in CMV immunosurveillance and revisit CMV-induced TCR reshaping in the era of NGS. Finally, we will demonstrate the favorable and unfavorable effects of CMV reactive \u03b3\u03b4 T cells post-transplantation.", "doi": "10.3390/v13061031", "pmid": "34072610", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8228273"}, {"db": "pii", "key": "v13061031"}], "notes": [], "created": "2026-08-21T13:05:13.840Z", "modified": "2026-08-21T13:05:13.910Z"}, {"entity": "publication", "iuid": "fa9c5d1a569f468ebda68f67a515d3b9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fa9c5d1a569f468ebda68f67a515d3b9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fa9c5d1a569f468ebda68f67a515d3b9"}}, "title": "TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells.", "authors": [{"family": "Sekine", "given": "Takuya", "initials": "T", "orcid": "0000-0001-7649-0593", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d9a6eb8b1e3846938ac6ffeba8231be7.json"}}, {"family": "Perez-Potti", "given": "Andr\u00e9", "initials": "A", "orcid": "0000-0002-5998-5700", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f5137f08ce7b4632aa2409148852618f.json"}}, {"family": "Nguyen", "given": "Son", "initials": "S", "orcid": "0000-0002-0475-5158", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/563175eaba7148b7816b90dbcb8fa578.json"}}, {"family": "Gorin", "given": "Jean-Baptiste", "initials": "JB"}, {"family": "Wu", "given": "Vincent H", "initials": "VH", "orcid": "0000-0002-8640-6065", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fa6136ee64f340b98cd54dfedf1160d9.json"}}, {"family": "Gostick", "given": "Emma", "initials": "E", "orcid": "0000-0002-3628-5824", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6017423d47424552b7e50fc2ecd1f67b.json"}}, {"family": "Llewellyn-Lacey", "given": "Sian", "initials": "S", "orcid": "0000-0002-4703-0413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/af57bac759494750a2c88baeb95c90e0.json"}}, {"family": "Hammer", "given": "Quirin", "initials": "Q", "orcid": "0000-0003-2968-6061", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bd1d59f056c149db98064ff1b0b99ed6.json"}}, {"family": "Falck-Jones", "given": "Sara", "initials": "S"}, {"family": "Vangeti", "given": "Sindhu", "initials": "S", "orcid": "0000-0003-3404-6878", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f234a13fb4fb443693add36d86c273e5.json"}}, {"family": "Yu", "given": "Meng", "initials": "M"}, {"family": "Smed-S\u00f6rensen", "given": "Anna", "initials": "A"}, {"family": "Gaballa", "given": "Ahmed", "initials": "A", "orcid": "0000-0002-5277-5129", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b062c2e7638440919938a93892cf7848.json"}}, {"family": "Uhlin", "given": "Michael", "initials": "M", "orcid": "0000-0002-2177-6727", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/116cfe482bb941159ee2e7175f1cd095.json"}}, {"family": "Sandberg", "given": "Johan K", "initials": "JK", "orcid": "0000-0002-6275-0750", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d33bfbd945e647ac82e2d2699df02cb9.json"}}, {"family": "Brander", "given": "Christian", "initials": "C"}, {"family": "Nowak", "given": "Piotr", "initials": "P", "orcid": "0000-0003-2747-0734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1b916fcba1024b208ed996cf957f499c.json"}}, {"family": "Goepfert", "given": "Paul A", "initials": "PA", "orcid": "0000-0001-8441-5737", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3914cf27200d4846b1cb5c505486fe95.json"}}, {"family": "Price", "given": "David A", "initials": "DA", "orcid": "0000-0001-9416-2737", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/17fa6bdd651d4efb93f267863eda54fc.json"}}, {"family": "Betts", "given": "Michael R", "initials": "MR", "orcid": "0000-0002-7690-1484", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c646f9a798841e6aefdbff38bad73b3.json"}}, {"family": "Buggert", "given": "Marcus", "initials": "M", "orcid": "0000-0003-0633-1719", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cf1bb88eef764f8bb81bdd6d8a231113.json"}}], "type": "journal article", "published": "2020-07-03", "journal": {"title": "Sci Immunol", "issn": "2470-9468", "volume": "5", "issue": "49", "issn-l": "2470-9468"}, "abstract": "CD8+ T cell exhaustion is a hallmark of many cancers and chronic infections. In mice, T cell factor 1 (TCF-1) maintains exhausted CD8+ T cell responses, whereas thymocyte selection-associated HMG box (TOX) is required for the epigenetic remodeling and survival of exhausted CD8+ T cells. However, it has remained unclear to what extent these transcription factors play analogous roles in humans. In this study, we mapped the expression of TOX and TCF-1 as a function of differentiation and specificity in the human CD8+ T cell landscape. Here, we demonstrate that circulating TOX+ CD8+ T cells exist in most humans, but that TOX is not exclusively associated with exhaustion. Effector memory CD8+ T cells generally expressed TOX, whereas naive and early-differentiated memory CD8+ T cells generally expressed TCF-1. Cytolytic gene and protein expression signatures were also defined by the expression of TOX. In the context of a relentless immune challenge, exhausted HIV-specific CD8+ T cells commonly expressed TOX, often in clusters with various activation markers and inhibitory receptors, and expressed less TCF-1. However, polyfunctional memory CD8+ T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) also expressed TOX, either with or without TCF-1. A similar phenotype was observed among HIV-specific CD8+ T cells from individuals who maintained exceptional immune control of viral replication. Collectively, these data demonstrate that TOX is expressed by most circulating effector memory CD8+ T cell subsets and not exclusively linked to exhaustion.", "doi": "10.1126/sciimmunol.aba7918", "pmid": "32620560", "labels": [], "xrefs": [{"db": "pii", "key": "5/49/eaba7918"}], "notes": [], "created": "2026-08-21T12:23:34.438Z", "modified": "2026-08-21T12:23:34.912Z"}, {"entity": "publication", "iuid": "38ab3ef241bf442d9c014e3e64758ef3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/38ab3ef241bf442d9c014e3e64758ef3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/38ab3ef241bf442d9c014e3e64758ef3"}}, "title": "CD8+ \u03b3\u03b4 T Cells Are More Frequent in CMV Seropositive Bone Marrow Grafts and Display Phenotype of an Adaptive Immune Response.", "authors": [{"family": "Gaballa", "given": "Ahmed", "initials": "A", "orcid": "0000-0002-5277-5129", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b062c2e7638440919938a93892cf7848.json"}}, {"family": "Arruda", "given": "Lucas C M", "initials": "LCM", "orcid": "0000-0002-8573-9618", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84d25ce6da6a4b21a4f147c6192386cd.json"}}, {"family": "R\u00e5destad", "given": "Emelie", "initials": "E", "orcid": "0000-0002-4011-7401", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6bbfa04b4fad4b3ea31a4a193e2e7c2d.json"}}, {"family": "Uhlin", "given": "Michael", "initials": "M", "orcid": "0000-0002-2177-6727", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/116cfe482bb941159ee2e7175f1cd095.json"}}], "type": "journal article", "published": "2019-12-06", "journal": {"title": "Stem Cells Int", "issn": "1687-966X", "volume": "2019", "pages": "6348060", "issn-l": null}, "abstract": "The role of gamma delta (\u03b3\u03b4) T cells in human cytomegalovirus (HCMV) immune surveillance has been the focus of research interest for years. Recent reports have shown a substantial clonal proliferation of \u03b3\u03b4 T cells in response to HCMV, shedding light on the adaptive immune response of \u03b3\u03b4 T cells. Nevertheless, most efforts have focused on V\u03b42neg \u03b3\u03b4 T cell subset while less attention has been given to investigate other less common \u03b3\u03b4 T cell subsets. In this regard, a distinct subpopulation of \u03b3\u03b4 T cells that expresses the CD8 coreceptor (CD8+ \u03b3\u03b4 T cells) has not been thoroughly explored. Whether it is implicated in HCMV response and its ability to generate adaptive response has not been thoroughly investigated. In this study, we combined flow cytometry and immune sequencing of the TCR \u03b3-chain (TRG) to analyze in-depth bone marrow (BM) graft \u03b3\u03b4 T cells from CMV seropositive (CMV+) and CMV seronegative (CMV-) donors. We showed that the frequency of CD8+ \u03b3\u03b4 T cells was significantly higher in CMV+ grafts compared to CMV- grafts (P < 0.001). Further characterization revealed that CD8+ \u03b3\u03b4 T cells from CMV+ grafts express V\u03b39- and preferentially differentiated from a naive to terminal effector memory phenotype (CD27low/-CD45RO-). In line with these findings, TRG immune sequencing revealed clonal focusing and reduced usage of the V\u03b39/JP gene segment in a CMV+ graft. Furthermore, CD8+ \u03b3\u03b4 T cells showed an enhanced response to TCR/CD3 and cytokine stimulation in contrast to CD8- \u03b3\u03b4 T cells. We conclude that \u03b3\u03b4 T cells in BM grafts are reshaped by donor CMV serostatus and highlight the potential adaptive role of CD8+ \u03b3\u03b4 T cells in HCMV immune response.", "doi": "10.1155/2019/6348060", "pmid": "31885619", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6925825"}], "notes": [], "created": "2026-08-21T12:28:26.405Z", "modified": "2026-08-21T12:28:26.565Z"}, {"entity": "publication", "iuid": "207a761f257c44108404dbc8272eb3e7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/207a761f257c44108404dbc8272eb3e7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/207a761f257c44108404dbc8272eb3e7"}}, "title": "T-cell frequencies of CD8+ \u03b3\u03b4 and CD27+ \u03b3\u03b4 cells in the stem cell graft predict the outcome after allogeneic hematopoietic cell transplantation.", "authors": [{"family": "Gaballa", "given": "Ahmed", "initials": "A", "orcid": "0000-0002-5277-5129", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b062c2e7638440919938a93892cf7848.json"}}, {"family": "Stikvoort", "given": "Arwen", "initials": "A"}, {"family": "\u00d6nfelt", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Mattsson", "given": "Jonas", "initials": "J"}, {"family": "Sundin", "given": "Mikael", "initials": "M", "orcid": "0000-0002-9871-0961", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ac33ee541ac44e59158cfed73f4992d.json"}}, {"family": "Watz", "given": "Emma", "initials": "E"}, {"family": "Uhlin", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2019-10-00", "journal": {"title": "Bone Marrow Transplant", "issn": "1476-5365", "volume": "54", "issue": "10", "pages": "1562-1574", "issn-l": null}, "abstract": "The impact of intra-graft T cells on the clinical outcome after allogeneic hematopoietic cell transplantation has been investigated. Most previous studies have focused on the role of \u03b1\u03b2 cells while \u03b3\u03b4 cells have received less attention. It has been an open question whether \u03b3\u03b4 cells are beneficial or not for patient outcome, especially with regards to graft versus host disease. In this study, graft composition of \u03b3\u03b4 cell subsets was analyzed and correlated to clinical outcome in 105 recipients who underwent allogeneic hematopoietic cell transplantation between 2013 and 2016. We demonstrate for the first time that grafts containing higher T-cell proportions of CD8+\u03b3\u03b4 cells were associated with increased cumulative incidence of acute graft versus host disease grade II-III (50% vs 22.6%; P = 0.008). Additionally, graft T-cell frequency of CD27+\u03b3\u03b4 cells was inversely correlated with relapse (P = 0.006) and CMV reactivation (P = 0.05). We conclude that clinical outcome after allogeneic hematopoietic cell transplantation is influenced by the proportions of distinct \u03b3\u03b4 cell subsets in the stem cell graft. We also provide evidence that CD8+\u03b3\u03b4 cells are potentially alloreactive and may play a role in acute graft versus host disease. This study illustrates the importance of better understanding of the role of distinct subsets of \u03b3\u03b4 cells in allogeneic hematopoietic cell transplantation.", "doi": "10.1038/s41409-019-0462-z", "pmid": "30723262", "labels": [], "xrefs": [{"db": "pii", "key": "10.1038/s41409-019-0462-z"}], "notes": [], "created": "2026-08-20T08:49:04.034Z", "modified": "2026-08-20T08:49:04.188Z"}, {"entity": "publication", "iuid": "9aeba8acc1a848be80d9edceafbd406e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9aeba8acc1a848be80d9edceafbd406e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9aeba8acc1a848be80d9edceafbd406e"}}, "title": "Graft \u03b3\u03b4 TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution.", "authors": [{"family": "Arruda", "given": "Lucas C M", "initials": "LCM", "orcid": "0000-0002-8573-9618", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84d25ce6da6a4b21a4f147c6192386cd.json"}}, {"family": "Gaballa", "given": "Ahmed", "initials": "A", "orcid": "0000-0002-5277-5129", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b062c2e7638440919938a93892cf7848.json"}}, {"family": "Uhlin", "given": "Michael", "initials": "M", "orcid": "0000-0002-2177-6727", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/116cfe482bb941159ee2e7175f1cd095.json"}}], "type": "journal article", "published": "2019-03-15", "journal": {"title": "J. Immunol.", "issn": "1550-6606", "volume": "202", "issue": "6", "pages": "1859-1870", "issn-l": "0022-1767"}, "abstract": "Although the impact of donor graft composition on clinical outcomes after hematopoietic stem cell transplantation (HSCT) has been studied, little is known about the role of intragraft \u03b3\u03b4 TCR repertoire on clinical outcomes following HSCT. Using a high-throughput sequencing platform, we sought to analyze the TCR \u03b3-chain (TRG) repertoire of \u03b3\u03b4 T cells within donor stem cell grafts and address its potential impact on clinical response in the corresponding patients. A total of 20 peripheral blood stem cell grafts were analyzed, and donors were classified as CMV+/- The respective acute myeloid leukemia recipients were followed for disease relapse and acute graft-versus-host disease (aGvHD) development post-HSCT. In all samples, TRG repertoire showed a reduced diversity and displayed overrepresented clones. This was more prominent in grafts from CMV+ donors, which presented a more private repertoire, lower diversity, skewed distribution, and reduced usage of the V9-JP pairing. Grafts given to nonrelapse patients presented a more public repertoire and increased presence of long sequence clonotypes. Variable-joining gene segment usage was not associated with aGvHD development, but a higher usage of V2-JP1 pairing and lower usage of V4-J2/V5-J2/V8-JP2 were observed in grafts given to nonrelapse patients. Our work identified five private overrepresented and one public CDR3 sequence (CATWDGPYYKKLF) associated with CMV infection, in addition to 12 highly frequent public sequences present exclusively in grafts given to nonrelapse patients. Our findings show that, despite CMV infection reshaping the TRG repertoire, TRG composition is not associated with aGvHD development, and several public sequences are associated with clinical remission.", "doi": "10.4049/jimmunol.1801448", "pmid": "30710048", "labels": [], "xrefs": [{"db": "pii", "key": "jimmunol.1801448"}], "notes": [], "created": "2026-08-21T13:06:12.037Z", "modified": "2026-08-21T13:06:12.081Z"}]}