{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T08:07:10Z","timestamp":1776586030948,"version":"3.51.2"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005375","name":"Latvian Council of Science, Fundamental and Applied Research Project","doi-asserted-by":"publisher","award":["Izp-2022\/1-0080"],"award-info":[{"award-number":["Izp-2022\/1-0080"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Chronic lymphocytic leukemia (CLL) is associated with immune dysfunction, but how disease-intrinsic mechanisms in treatment-naive patients influence the coordination of adaptive responses to novel antigens remains unclear. Here, we assessed SARS-CoV-2-specific antibody and T cell immunity in 38 treatment-naive CLL patients and 13 healthy controls (HCs) following vaccination. Despite significantly reduced total immunoglobulin levels compared to HCs, 94.7% of CLL patients developed SARS-CoV-2-specific IgG, and 89.5% mounted IgA responses, with serum titers comparable to those of HCs. Virus-specific T cell responses, measured by IFN-\u03b3 release following antigen stimulation, were detected in 78.9% of patients. CLL patients had significantly more circulating CD4+ T follicular helper (Tfh) and T follicular regulatory (Tfr) cells than HCs. These expansions correlated with B cell abundance, which, in untreated CLL, predominantly reflects malignant B cells. Notably, Tfh cell frequencies and absolute counts were highest in patients lacking a SARS-CoV-2-specific T cell response, indicating a decoupling between Tfh expansion and functional antiviral immunity. Overall, these findings demonstrate that while SARS-CoV-2-specific immune responses are largely preserved in treatment-naive CLL patients, disease-driven alterations in T cell composition may compromise the coordination and quality of antigen-specific T cell-mediated immunity.<\/jats:p>","DOI":"10.3390\/pathogens14090890","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T09:51:21Z","timestamp":1757065881000},"page":"890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Attenuated SARS-CoV-2-Specific T Cell Responses Are Associated with T Follicular Helper Cell Expansion in Treatment-Naive Chronic Lymphocytic Leukemia Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"Baiba","family":"\u0160lisere","sequence":"first","affiliation":[{"name":"Department of Internal Diseases, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"},{"name":"Chemotherapy and Hematology Clinic, R\u012bga East University Hospital, LV-1038 Riga, Latvia"},{"name":"Joint Laboratory, Pauls Stradi\u0146\u0161 Clinical University Hospital, LV-1002 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3501-9059","authenticated-orcid":false,"given":"Roberts","family":"K\u0101rkli\u0146\u0161","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alla","family":"Rivkina","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"},{"name":"Chemotherapy and Hematology Clinic, R\u012bga East University Hospital, LV-1038 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6682-6372","authenticated-orcid":false,"given":"Sandra","family":"Lejniece","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"},{"name":"Chemotherapy and Hematology Clinic, R\u012bga East University Hospital, LV-1038 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2021-2938","authenticated-orcid":false,"given":"Krist\u012bne","family":"O\u013cei\u0146ika","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases, R\u012bga Stradi\u0146\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/S0140-6736(18)30422-7","article-title":"Chronic lymphocytic leukaemia","volume":"391","author":"Hallek","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1182\/blood-2015-03-567388","article-title":"Perturbation of the normal immune system in patients with CLL","volume":"126","author":"Forconi","year":"2015","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/cyto.b.21595","article-title":"Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project","volume":"94","author":"Rawstron","year":"2018","journal-title":"Cytom. 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