Clonal Expansion of CD8+ Effector T Cells in Childhood Tuberculosis

Abstract

The role of CD8+ T cells in human tuberculosis (TB) remains elusive. We analyzed the T cell repertoire and phenotype in 1) children with active TB (≤4 years), 2) healthy latently Mycobacterium tuberculosis-infected children, and 3) noninfected age-matched (tuberculin skin test-negative) controls. Ex vivo phenotyping of T cell subpopulations by flow cytometry revealed a significant increase in the proportion of CD8+CD45RO−CD62L−CD28−CD27− effector T cells (TEF) in the peripheral blood of children with active TB (22.1 vs 9.5% in latently M. tuberculosis-infected children, vs 8.5% in tuberculin skin test-negative controls). Analyses of TCR variable β-chains revealed markedly skewed repertoires in CD8+ TEF and effector memory T cells. Expansions were restricted to single TCR variable β-chains in individual donors indicating clonal growth. CDR3 spectratyping and DNA sequencing verified clonal expansion as the cause for CD8+ effector T cell enrichment in individual TB patients. The most prominent enrichment of highly similar TEF clones (>70% of CD8+ TEF) was found in two children with active severe TB. Therefore, clonal expansion of CD8+ TEF occurs in childhood TB with potential impact on course and severity of disease.