Mycobacterium tuberculosis-Specific CFP-10/ESAT-6 CD4 and CD8 T-Cell Non-IFN-γ+ Responses Are Common in Young Kenyan Children Despite Low Reported Tuberculosis Exposure.
| Title: | Mycobacterium tuberculosis-Specific CFP-10/ESAT-6 CD4 and CD8 T-Cell Non-IFN-γ+ Responses Are Common in Young Kenyan Children Despite Low Reported Tuberculosis Exposure. |
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| Authors: | LaCourse SM; Department of Global Health.; Division of Allergy and Infectious Diseases, Department of Medicine.; Department of Epidemiology, University of Washington, Seattle.; Escudero JN; Department of Global Health.; Whatney WE; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University.; Krish KN; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University.; Subuddhi A; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University.; Belauret S; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University.; Pearson RA; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University.; Cranmer LM; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.; Mecha J; Centre for Respiratory Diseases Research, Kenya Medical Research Institute.; Matemo D; Medical Research Department, Kenyatta National Hospital.; Maleche-Obimbo E; Department of Global Health.; Department of Paediatrics and Child Health, University of Nairobi.; Kinuthia J; Department of Global Health.; Medical Research Department, Kenyatta National Hospital.; Department of Reproductive Health, Kenyatta National Hospital, Nairobi, Kenya.; Richardson BA; Department of Global Health.; Department of Biostatistics.; John-Stewart G; Department of Global Health.; Division of Allergy and Infectious Diseases, Department of Medicine.; Department of Epidemiology, University of Washington, Seattle.; Department of Pediatrics, University of Washington, Seattle.; Day CL; Department of Microbiology and Immunology, Emory University School of Medicine.; Emory Vaccine Center, Emory University. |
| Source: | The Journal of infectious diseases [J Infect Dis] 2026 Apr 29; Vol. 233 (4), pp. e981-e989. |
| 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: | CD8-Positive T-Lymphocytes*/immunology ; CD4-Positive T-Lymphocytes*/immunology ; Mycobacterium tuberculosis*/immunology ; Tuberculosis*/immunology ; Tuberculosis*/epidemiology ; Tuberculosis*/diagnosis ; Antigens, Bacterial*/immunology ; Bacterial Proteins*/immunology; Kenya/epidemiology ; Interferon-gamma/metabolism ; HIV Infections/immunology ; Interleukin-2/metabolism ; Humans ; Infant ; Female ; Male ; Child, Preschool ; Cytokines |
| Abstract: | Background: Reduced early-life interferon-γ (IFN-γ) production capacity may limit sensitivity of IFN-γ release assays to detect Mycobacterium tuberculosis (Mtb)-specific responses in young children. Measuring non-IFN-γ cytokine responses may improve detection.; Methods: Mononuclear cells isolated from peripheral blood from children exposed to HIV but uninfected and children unexposed to HIV in Western Kenya were collected at 6 to 10 weeks, and 12 and 24 months of age. Cells were incubated overnight with Mtb-specific CFP-10/ESAT-6 peptides and Staphylococcus enterotoxin B (positive control). CD4 and CD8 T-cell expression of IFN-γ and IL-2 and TNF cytokines was measured by flow cytometry.; Results: Among 213 children, 28.6% had CFP-10/ESAT-6-specific CD4 and/or CD8 responses through 24 months. No children with Mtb-specific responses had a reported tuberculosis exposure. Mtb-specific non-IFN-γ+ responses (IL-2+ and/or TNF+) were more common than IFN-γ+ responses (26.3% vs 10.3%, P < .001). Non-IFN-γ cytokines alone identified 18.3% of children, compared with 2.4% identified by IFN-γ+ responses alone (P < .001). Prevalence of Mtb-specific responses was similar regardless of HIV exposure (HIV exposed, 31.5%; HIV unexposed, 25.5%, P = .33). At 6 to 10 weeks, children were more likely to have non-IFN-γ+ than IFN-γ+ responses to the positive control (96.3% vs 77.8%, P = .004); by 24 months, all children mounted both IFN-γ+ and non-IFN-γ+ responses.; Conclusions: Mtb-specific CD4/CD8 responses were common among Kenyan children through 24 months, despite limited reported tuberculosis exposures. Non-IFN-γ+ cytokine expression identified substantially more children than IFN-γ+ alone, suggesting current IFN-γ release assays may miss early-life Mtb-specific responses.; (© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America.) |
| Competing Interests: | Potential conflicts of interest. All authors: No reported conflicts. |
| Grant Information: | K23 AI120793 United States AI NIAID NIH HHS; P30 AI168386 United States AI NIAID NIH HHS; R01 AI142647 United States AI NIAID NIH HHS; National Institute of Allergy and Infectious Diseases; United States TR NCATS NIH HHS; K23AI120793 United States NH NIH HHS; R01AI142647 United States NH NIH HHS; P30AI168386 United States NH NIH HHS; R21HD098746 United States NH NIH HHS; UL1TR000423 United States NH NIH HHS |
| Contributed Indexing: | Keywords: Mycobacterium tuberculosis infection; CD4 and CD8 T cell; HIV; cytokines; interferon-γ release assay |
| Substance Nomenclature: | 82115-62-6 (Interferon-gamma); 0 (Antigens, Bacterial); 0 (Bacterial Proteins); 0 (ESAT-6 protein, Mycobacterium tuberculosis); 0 (esxB protein, Mycobacterium); 0 (Cytokines); 0 (Interleukin-2) |
| Entry Date(s): | Date Created: 20260122 Date Completed: 20260429 Latest Revision: 20260429 |
| Update Code: | 20260430 |
| PubMed Central ID: | PMC13033399 |
| DOI: | 10.1093/infdis/jiag039 |
| PMID: | 41566843 |
| Database: | MEDLINE |
Journal Article