Clonal expansion of CD8+ effector T cells in childhood tuberculosis.
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 (< or =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 (T(EF)) 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 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.
Jacobsen
Marc
M
Department of Immunology, Max Planck Institute for Infection Biology, University Hospital Charité, Berlin, Germany. jacobsen@mpiib-berlin.mpg.de
Detjen
Anne K
AK
Mueller
Henrik
H
Gutschmidt
Andrea
A
Leitner
Sandra
S
Wahn
Ulrich
U
Magdorf
Klaus
K
Kaufmann
Stefan H E
SH
D000595:Amino Acid Sequence; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002675:Child, Preschool; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta