Clonal expansion of CD8+ effector T cells in childhood tuberculosis

The role of CD8(+) T cells in human tuberculosis JB) remains elusive. We analyzed the T cell repertoire and phenotype in 1) children with active TB (:54 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 (T-EF) in the peripherai 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 beta-chains revealed markedly skewed repertoires in CD8(+) T-EF and effector memory T cells. Expansions were restricted to single TCR variable beta-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 T-EF clones (>70% of CD8(+) T-EF) was found in two children with active severe TB. Therefore, clonal expansion of CD8(+) T-EF occurs in childhood TB with potential impact on course and severity of disease.