Decreased expression of CD3zeta and nuclear transcription factor kappa B in patients with pulmonary tuberculosis: potential mechanisms and reversibility with treatment

J Infect Dis. 2006 Nov 15;194(10):1385-93. doi: 10.1086/508200. Epub 2006 Oct 4.


Background: The protective immune response against Mycobacterium tuberculosis relies both on antigen-presenting cells and on T lymphocytes. In patients with different forms of tuberculosis, varying degrees of T cell function--ranging from positive delayed-type hypersensitivity, in asymptomatic infected healthy individuals, to the absence of the response, in patients with miliary or pulmonary tuberculosis (PTB)--have been reported. The decreased expression of CD3zeta reported in T cells from patients with either cancer or leprosy has provided possible explanations for the altered immune response observed in these diseases.

Methods: The present study aimed to compare the expression of CD3zeta , nuclear transcription factor- kappa B (NF- kappa B), arginase activity, and cytokine production in 20 patients with PTB, in 20 tuberculin-positive asymptomatic subjects, and in 14 tuberculin-negative control subjects.

Results: Compared with those in tuberculin (purified protein derivative)-negative control subjects, peripheral-blood T lymphocytes from patients with active PTB had significantly (P < .001) decreased expression of CD3zeta and absence of the p65/p50 heterodimer of NF- kappa B. These alterations were reversed only in patients who responded to treatment. Also reported here for the first time is that the presence of arginase activity in peripheral-blood mononuclear-cell lysates of patients with PTB parallels high production of interleukin-10.

Conclusions: The presence of arginase could, in part, explain the decreased expression of CD3zeta . These findings provide a novel mechanism that may explain the T cell dysfunction observed in patients with PTB.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arginase / analysis
  • CD3 Complex / biosynthesis*
  • Cytokines / analysis
  • Electrophoretic Mobility Shift Assay
  • Female
  • Flow Cytometry
  • Gene Expression*
  • Humans
  • Hypersensitivity, Delayed
  • Leukocytes, Mononuclear / enzymology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • NF-kappa B / biosynthesis*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics as Topic
  • T-Lymphocytes / chemistry
  • Tuberculin Test
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / immunology*


  • CD3 Complex
  • CD3 antigen, zeta chain
  • Cytokines
  • NF-kappa B
  • RNA, Messenger
  • Arginase