Region of difference 1 antigen-specific CD4+ memory T cells correlate with a favorable outcome of tuberculosis

Delia Goletti, Ornella Butera, Federica Bizzoni, Rita Casetti, Enrico Giradi, Fabrizio Poccia

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Interferon (IFN)-γ response to region of difference (RD) 1 proteins (culture filtrate 10 and early secreted antigenic target 6) or overlapping peptides is a novel diagnostic marker of tuberculosis (TB) infection. Because we have recently shown that the response to certain peptides selected from RD1 allows discrimination between active TB (A-TB) and successfully treated TB (T-TB), we analyzed here the effector memory T cell profile and RD1-specific responses under the same clinical conditions. Methods. T cell responses to RD1 antigens were analyzed in patients with either severe or mild A-TB (classified on the basis of radiological lesions) and in 2 sets of healthy control subjects-those who had been successfully treated (the T-TB control subjects) and those whose tuberculin skin test (TST) results were negative (the TST-negative control subjects). IFN-γ-producing CD4 + effector T cells were monitored by flow-cytometric analysis and ex vivo enzyme-linked immunospot (ELISPOT) assay, whereas a "cultured" ELISPOT assay was used to determine the frequency of memory T cells. Results. In the patients with severe A-TB, both CD4-mediated effector memory and central memory responses to the selected RD1 peptides were almost absent, whereas these responses were found in the majority of the patients with mild A-TB. In contrast, recognition of the selected RD1 peptides was detected in the T-TB control subjects only by expanding the central memory T cell pool. Conclusions. These data suggest a protective role for RD1 peptide-specific CD4+ effector T cells, which undergo clonal expansion during Mycobacterium tuberculosis replication and then a contraction phase after disease resolution, culminating in the generation of CD4+ memory T cells.

Original languageEnglish
Pages (from-to)984-992
Number of pages9
JournalJournal of Infectious Diseases
Volume194
Issue number7
DOIs
Publication statusPublished - Oct 1 2006

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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