{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:25:13Z","timestamp":1770459913497,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,20]]},"group-title":"Immunology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["R01CA263324"],"award-info":[{"award-number":["R01CA263324"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Memory T cell inflation is a distinctive immunological phenomenon observed during persistent viral infections, such as Cytomegalovirus (CMV). Unlike conventional memory T cell responses, which contract after infection resolution, a subset of CMV-specific T cells undergoes a progressive and sustained expansion, termed \u201cinflation\u201d, which is thought to be critical for long-term immune surveillance. The molecular mechanisms that govern memory T cell inflation remain incompletely understood, yet they are pivotal for understanding immune persistence and designing strategies against chronic viral infections. In this study, we investigate the role of MAP kinase-activated protein kinase 2 (MK2), a key downstream effector of p38 MAPK signaling, in regulating T cell responses during murine CMV (MCMV) infection. Using MK2 knockout (MK2-KO) mice, we demonstrate that MK2 deficiency alters the dynamics of MCMV-specific CD8\u207a T cell responses without impairing viral control or tissue replication. MK2 deficiency led to a reduction in non-inflationary MCMV-specific CD8\u207a T cells during the acute phase, followed by enhanced expansion of inflationary CD8\u207a T cell subsets during persistence. Furthermore, MK2-KO mice exhibited impaired effector differentiation, as evidenced by decreased expression of the terminal differentiation marker KLRG1 on MCMV-specific CD8\u207a T cells. Collectively, these findings identify MK2 as a pivotal regulator of CD8\u207a T cell magnitude, kinetics, and phenotype during both acute and chronic MCMV infection. By elucidating the role of MK2 in the regulation of memory T cell inflation, this study provides new mechanistic insight into immune regulation with implications for vaccination, chronic infection, and immune aging.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical abstract<\/jats:title>\n                  <jats:p>\n                    The graphical abstract was created using BioRender (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/biorender.com\/\">https:\/\/biorender.com\/<\/jats:ext-link>\n                    ).\n                  <\/jats:p>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"699974v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.16.699974","type":"posted-content","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T01:45:18Z","timestamp":1768959918000},"source":"Crossref","is-referenced-by-count":0,"title":["MAPKAP Kinase 2 Orchestrates Memory T Cell Inflation in Cytomegalovirus Infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7574-1378","authenticated-orcid":false,"given":"Eleni","family":"Panagioti","sequence":"first","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Precision Cancer Medicine, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi Wen","family":"Kong","sequence":"additional","affiliation":[{"name":"Center for Precision Cancer Medicine, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Makakova","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noe B.","family":"Mercado","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Legorreta Cancer Center, Brown University, Providence, RI, USA"},{"name":"The Warren Alpert Medical School, Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean Edward","family":"Lawler","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Legorreta Cancer Center, Brown University, Providence, RI, USA"},{"name":"The Warren Alpert Medical School, Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Yaffe","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"},{"name":"Center for Precision Cancer Medicine, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles H.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2026020608551570000_2026.01.16.699974v1.1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-023-01471-y","article-title":"T cells in health and disease","volume":"8","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"9","key":"2026020608551570000_2026.01.16.699974v1.2","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/s41423-024-01186-2","article-title":"Immune surveillance of cytomegalovirus in tissues","volume":"21","year":"2024","journal-title":"Cell Mol Immunol"},{"key":"2026020608551570000_2026.01.16.699974v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-022-13971-7"},{"key":"2026020608551570000_2026.01.16.699974v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00582-z"},{"key":"2026020608551570000_2026.01.16.699974v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104732"},{"key":"2026020608551570000_2026.01.16.699974v1.6","doi-asserted-by":"crossref","unstructured":"Chiavarini M , Genga A , Ricciotti GM , D\u2019Errico MM , Barbadoro P. 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