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Clonal Expansion of CD8⁺ Effector T Cells in Childhood Tuberculosis¹

Marc Jacobsen^2,*, Anne K. Detjen, Henrik Mueller^*, Andrea Gutschmidt^*, Sandra Leitner^*, Ulrich Wahn, Klaus Magdorf and Stefan H. E. Kaufmann^*

^* Department of Immunology, Max Planck Institute for Infection Biology, and Department of Pediatric Pneumology and Immunology, University Hospital Charité, Berlin, Germany

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 (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 -chains revealed markedly skewed repertoires in CD8⁺ T_EF and effector memory T cells. Expansions were restricted to single TCR variable -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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported, in part, by financial support from the Bill and Melinda Gates Foundation, Grand Challenge 6 (to M.J. and S.H.E.K.), and from the Fonds Chemie (to S.H.E.K.).

² Address correspondence and reprint requests to Dr. Marc Jacobsen, Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany. E-mail address: jacobsen{at}mpiib-berlin.mpg.de

³ Abbreviations used in this paper: TB, tuberculosis; LTBI, latently Mycobacterium tuberculosis infected; T_naive, naive T cell; T_CM, central memory T cell; T_EM, effector memory T cell; T_EF, effector T cell; TST, tuberculin skin test.

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