{"id":32485,"date":"2025-05-14T18:51:43","date_gmt":"2025-05-14T16:51:43","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/05\/14\/virus-specific-cd4-t-cells-contribute-to-clearance-of-human-metapneumovirus-despite-exhibiting-an-impaired-phenotype\/"},"modified":"2025-05-14T18:51:43","modified_gmt":"2025-05-14T16:51:43","slug":"virus-specific-cd4-t-cells-contribute-to-clearance-of-human-metapneumovirus-despite-exhibiting-an-impaired-phenotype","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/05\/14\/virus-specific-cd4-t-cells-contribute-to-clearance-of-human-metapneumovirus-despite-exhibiting-an-impaired-phenotype\/","title":{"rendered":"Virus-specific CD4+ T cells contribute to clearance of human metapneumovirus despite exhibiting an impaired phenotype"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 May 14:vkaf076. doi: 10.1093\/jimmun\/vkaf076. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Human metapneumovirus (HMPV) is a leading cause of respiratory tract infection in pediatric, elderly, and immunocompromised populations. Clearance of HMPV relies primarily on the destruction of infected cells by cytotoxic CD8+ T cells. However, signals provided by CD4+ helper T cells significantly impact the magnitude and effectiveness of CD8+ T cells. The role of CD4+ helper T cells in the immune response to HMPV is largely unknown. Antibody-mediated depletion of CD4+ T cells in a mouse model of acute infection led to delayed viral clearance and enhanced PD-1 expression on virus-specific CD8+ T cells. In accord with CD4 depletion experiments, blocking of CD40L reduced viral control and CD8+ T cell responses while stimulation of this pathway with an agonist antibody decreased the duration of infection. We identified a dominant CD4+ T cell epitope in the viral nucleoprotein and constructed the first MHC-II tetramer for HMPV. Analysis of pulmonary T cells revealed that virus-specific cells peak on day 10 post-infection and were TH1-skewed. Additionally, virus-specific CD4+ T cells displayed phenotypic and functional markers of impairment, including inhibitory receptor co-expression and prolonged PD-1 upregulation. However, genetic ablation of PD-1 signaling did not improve virus-specific CD4+ T cell functionality. Further characterization of virus-specific CD4+ helper T cells, their regulation by PD-1, and their role in CD8+ T cell impairment will provide new insights that aid in the design of effective vaccines for HMPV.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40365919\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250514125136&amp;v=2.18.0.post9+e462414\">40365919<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf076\">10.1093\/jimmun\/vkaf076<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 May 14:vkaf076. doi: 10.1093\/jimmun\/vkaf076. Online ahead of print. ABSTRACT Human metapneumovirus (HMPV) is a leading cause of respiratory tract infection in pediatric, elderly, and immunocompromised populations. Clearance of HMPV relies primarily on the destruction of infected cells by cytotoxic CD8+ T cells. However, signals provided by CD4+ helper T cells significantly impact &#8230; <a title=\"Virus-specific CD4+ T cells contribute to clearance of human metapneumovirus despite exhibiting an impaired phenotype\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/05\/14\/virus-specific-cd4-t-cells-contribute-to-clearance-of-human-metapneumovirus-despite-exhibiting-an-impaired-phenotype\/\" aria-label=\"Read more about Virus-specific CD4+ T cells contribute to clearance of human metapneumovirus despite exhibiting an impaired phenotype\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-32485","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/32485","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=32485"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/32485\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=32485"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=32485"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=32485"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}