| 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 |
| Authors: |
LaCourse, Sylvia M; Escudero, Jaclyn N; Whatney, Wendy E; Krish, Krista N; Subuddhi, Arijita; Belauret, Sara; Pearson, Rachel A; Cranmer, Lisa Marie; Mecha, Jerphason; Matemo, Daniel; Maleche-Obimbo, Elizabeth; Kinuthia, John; Richardson, Barbra A; John-Stewart, Grace; Day, Cheryl L |
| Contributors: |
National Institute of Allergy and Infectious Diseases; National Center for Advancing Translational Sciences; National Institutes of Health |
| Source: |
The Journal of Infectious Diseases ; ISSN 0022-1899 1537-6613 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2026 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/infdis/jiag039 |
| DOI: |
10.1093/infdis/jiag039/66527071/jiag039.pdf |
| Availability: |
https://doi.org/10.1093/infdis/jiag039; https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiag039/66527071/jiag039.pdf |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.FCEC8063 |
| Database: |
BASE |