Patterns and Cofactors of Polyfunctional Mycobacteria-Specific T-Cell Response Restoration Following 6-Month Antiretroviral Treatment in Children With HIV.
| Title: | Patterns and Cofactors of Polyfunctional Mycobacteria-Specific T-Cell Response Restoration Following 6-Month Antiretroviral Treatment in Children With HIV. |
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| Authors: | Day CL; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University, Atlanta, Georgia.; Njuguna IN; Department of Medical Research, Kenyatta National Hospital, Nairobi, Kenya.; Department of Global Health, University of Washington, Seattle.; Cranmer LM; Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta.; Children's Healthcare of Atlanta, Georgia.; Whatney WE; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University, Atlanta, Georgia.; Pearson RA; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University, Atlanta, Georgia.; Lindestam Arlehamn CS; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, California.; Center for Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.; Sette A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, California.; Department of Medicine, University of California San Diego.; LaCourse SM; Department of Global Health, University of Washington, Seattle.; Division of Allergy and Infectious Diseases, Department of Medicine.; Department of Epidemiology, University of Washington, Seattle.; Escudero JN; Department of Global Health, University of Washington, Seattle.; Sasser LE; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University, Atlanta, Georgia.; Mugo C; Department of Medical Research, Kenyatta National Hospital, Nairobi.; Okinyi HM; Department of Pediatrics and Child Health, University of Nairobi, Kenya.; Maleche-Obimbo E; Department of Pediatrics and Child Health, University of Nairobi, Kenya.; Wamalwa DC; Department of Pediatrics and Child Health, University of Nairobi, Kenya.; John-Stewart GC; Department of Global Health, University of Washington, Seattle.; Division of Allergy and Infectious Diseases, Department of Medicine.; Department of Epidemiology, University of Washington, Seattle.; Department of Pediatrics, University of Washington, Seattle. |
| Source: | The Journal of infectious diseases [J Infect Dis] 2025 Apr 15; Vol. 231 (4), pp. 957-966. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE |
| Imprint Name(s): | Publication: Jan. 2011- : Oxford : Oxford University Press; Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press |
| MeSH Terms: | Anti-HIV Agents*/therapeutic use ; Anti-Retroviral Agents*/therapeutic use ; HIV Infections*/drug therapy ; HIV Infections*/immunology ; HIV Infections*/complications; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cytokines/metabolism ; Mycobacterium tuberculosis/immunology ; Tuberculosis/immunology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Kenya ; Lymphocyte Activation ; Randomized Controlled Trials as Topic ; Enterotoxins |
| Abstract: | Background: Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children with HIV (CHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CHIV.; Methods: CD4 and CD8 T-cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral blood mononuclear cells from CHIV enrolled in the PUSH study (NCT02063880) in Nairobi, Kenya. T-cell expression of cytokines and activation-induced markers were measured following stimulation of peripheral blood mononuclear cells with a pool of 300 peptides from TB (MTB300) or staphylococcal enterotoxin B.; Results: Among 47 CHIV (median age, 1.5 years), staphylococcal enterotoxin B-induced Th1 cytokine+ and activation-induced marker+ CD4 cell frequencies increased significantly after 6 months of ART. Although MTB300-specific CD4 and CD8 cell frequency did not increase after ART, polyfunctional capacity of MTB300-specific CD4 cells expressing combinations of Th1 cytokines with CD40L increased significantly after ART. Baseline age, immune activation, and effector memory CD4 levels were associated with less restoration of MTB300-specific polyfunctional CD4 cells, whereas CD4 percentage and levels of naive CD4 cells following ART were associated with improved MTB300-specific polyfunctional capacity.; Conclusions: Despite increases in Th1 cytokine production, deficits in mycobacteria-specific CD4 cells persisted 6 months after ART, with higher deficits in older CHIV with more immunosuppression, higher immune activation, and lower proportion of naive CD4 cells. These findings may explain persistent TB risk during early ART among CHIV and identify those at highest risk.; (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| Competing Interests: | Potential conflicts of interest. All authors: No reported conflicts. |
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| Grant Information: | ; R01AI142647 National Institute of Allergy and Infectious Diseases; K23 AI143479 United States AI NIAID NIH HHS; R01 HD023412 United States HD NICHD NIH HHS; P30 AI168386 United States AI NIAID NIH HHS; P30AI168386 Emory/Georgia TB Research Advancement Center; R01 AI142647 United States AI NIAID NIH HHS; K23 AI120793 United States AI NIAID NIH HHS; R01HD023412 Eunice Kennedy Shriver National Institute of Child Health and Human Development |
| Contributed Indexing: | Keywords: CD4 T cell; HIV; antiretroviral therapy; immune reconstitution; tuberculosis |
| Substance Nomenclature: | 0 (Anti-HIV Agents); 0 (Anti-Retroviral Agents); 0 (Cytokines); 39424-53-8 (enterotoxin B, staphylococcal); 0 (Enterotoxins) |
| Entry Date(s): | Date Created: 20241218 Date Completed: 20250415 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11998549 |
| DOI: | 10.1093/infdis/jiae630 |
| PMID: | 39693245 |
| Database: | MEDLINE |
Journal Article