ArticleJournal of immunology (Baltimore, Md. : 1950)2016
IL-12-Dependent Cytomegalovirus-Specific CD4+ T Cell Proliferation, T-bet Induction, and Effector Multifunction during Primary Infection Are Key Determinants for Early Immune Control.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- The search for peripheral tolerance in lung transplantation.Current opinion in pulmonary medicine · 2025Review
- Oncolytic cytomegaloviruses expressing EGFR-retargeted fusogenic glycoprotein complex and drug-controllable interleukin 12.Cell reports. Medicine · 2025Article
- Potential of Interleukin (IL)-12 Group as Antivirals: Severe Viral Disease Prevention and Management.International journal of molecular sciences · 2023Review
- Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer.International journal of molecular sciences · 2023Article
- Prediction of herpes virus infections after solid organ transplantation: a prospective study of immune function.Frontiers in immunology · 2023Article
- Risk prediction of CMV reactivation after allogeneic stem cell transplantation using five non-HLA immunogenetic polymorphisms.Annals of hematology · 2022Article
- The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells.Cancer immunology, immunotherapy : CII · 2021Article
- Association between single nucleotide polymorphisms and viral load in congenital cytomegalovirus infection.Journal of mother and child · 2021Article
- Type-1 immunity and endogenous immune regulators predominate in the airway transcriptome during chronic lung allograft dysfunction.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- T cell repertoire remodeling following post-transplant T cell therapy coincides with clinical response.The Journal of clinical investigation · 2019Article
- Early KLRG1Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Impaired Cytomegalovirus Immunity in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres.American journal of respiratory and critical care medicine · 2019Article
- Effect of Cytomegalovirus (CMV) and Ageing on T-Bet and Eomes Expression on T-Cell Subsets.International journal of molecular sciences · 2017Article
- CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function.Oncotarget · 2017Article
- HIV Suppression Restores the Lung Mucosal CD4+ T-Cell Viral Immune Response and Resolves CD8+ T-Cell Alveolitis in Patients at Risk for HIV-Associated Chronic Obstructive Pulmonary Disease.The Journal of infectious diseases · 2016Article
- Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection.PLoS pathogens · 2016Article
- Granzyme BGut microbesArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
CMV remains an important opportunistic pathogen in solid organ and hematopoietic cell transplantation, particularly in lung transplant recipients (LTRs). LTRs mismatched for CMV (donor(+)/recipient(-); D(+)R(-)) are at high risk for active CMV infection and increased mortality; however, the immune correlates of viral control remain incompletely understood. We prospectively studied 27 D(+)R(-) LTRs during primary CMV infection to determine whether acute CD4(+) T cell parameters differentiated the capacity for viral control during early chronic infection. Unexpectedly, the T-box transcription factor, T-bet, was expressed at low levels in CD4(+) compared with CD8(+) T cells during acute primary infection. However, the capacity for in vitro CMV phosphoprotein 65-specific proliferation and CD4(+)T-bet(+) induction differentiated LTR controllers from early viremic relapsers, correlating with granzyme B loading and effector multifunction. Furthermore, impaired CMV-specific proliferative responses from relapsers, along with T-bet, and effector function could be significantly rescued, most effectively with phosphoprotein 65 Ag and combined exogenous IL-2 and IL-12. Acute CD4(+) T cell CMV-specific proliferative and effector responses were highly IL-12-dependent in blocking studies. In addition, we generated monocyte-derived dendritic cells using PBMC obtained during primary infection from relapsers and observed impaired monocyte-derived dendritic cell differentiation, a reduced capacity for IL-12 production, but increased IL-10 production compared with controls, suggesting an APC defect during acute CMV viremia. Taken together, these data show an important role for CMV-specific CD4(+) effector responses in differentiating the capacity of high-risk LTRs to establish durable immune control during early chronic infection and provide evidence for IL-12 as a key factor driving these responses.
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