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

J Infect Dis. 2006 Oct 1;194(7):984-92. doi: 10.1086/507427. Epub 2006 Aug 30.


Background: Interferon (IFN)-gamma 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-gamma -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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Humans
  • Immunologic Memory*
  • Lymphocyte Activation
  • Male
  • Mycobacterium tuberculosis / physiology
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / immunology*
  • Prognosis
  • Severity of Illness Index
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / physiopathology


  • Antigens, Bacterial
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Peptides