title: Decreased CD4+ lymphocytes and innate immune responses in adults with previous extrapulmonary tuberculosis.
abstract: BACKGROUND
  CD4+ lymphocytes control Mycobacterium tuberculosis infection through cytokine-mediated macrophage activation. Extrapulmonary tuberculosis is presumably a marker of immunodeficiency, but cytokine responses have not been well studied in such patients.
  
  
  OBJECTIVE
  Assess immune defects in persons with previous extrapulmonary tuberculosis.
  
  
  METHODS
  In vitro cytokine responses of PBMCs from HIV-seronegative adults with previous extrapulmonary tuberculosis (n = 10) were compared with responses from persons with previous pulmonary tuberculosis (n = 24) and latent M tuberculosis infection (n = 30) in a case-control study.
  
  
  RESULTS
  Patients and controls did not differ according to age, sex, race, or monocytes. The median time between tuberculosis diagnosis and study entry was 72 and 122 weeks in extrapulmonary and pulmonary patients, respectively (P = .2). Median CD4+ counts were 660, 814, and 974 lymphocytes/mm3 in extrapulmonary, pulmonary, and latently infected patients, respectively (P = .03). At 48 hours, median unstimulated cytokine levels were uniformly lower in extrapulmonary patients than both sets of controls. These differences persisted after controlling for CD4+ count by linear regression analysis. Despite lower unstimulated levels, median TNF-alpha response was higher in patients with extrapulmonary and pulmonary tuberculosis than latently infected persons after stimulation with PHA 1% (P = .006) and PHA+IL-12 (1 ng/mL; P = .02); IL-10 remained low in patients with extrapulmonary tuberculosis after the same stimuli (P = .04 and .06, respectively). There was no primary immunodeficiency in the IL-12/23-IFN-gamma axis.
  
  
  CONCLUSIONS
  HIV-seronegative adults with previous extrapulmonary tuberculosis had lower CD4+ lymphocytes and unstimulated cytokine production. This suggests a subtle abnormality in innate immune function.
  
  
  CONCLUSIONS
  These characteristics could identify persons at risk for severe tuberculosis manifestations.
authors.affiliation: Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2605, USA.
authors.forename: Paulo R Z
authors.initials: PR
authors.lastname: Antas
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Judith
authors.initials: J
authors.lastname: Hackman
authors.forename: Linda
authors.initials: L
authors.lastname: Reeves-Hammock
authors.forename: Ayumi K
authors.initials: AK
authors.lastname: Shintani
authors.forename: Joshua
authors.initials: J
authors.lastname: Schiffer
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sterling
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology
chemical_list: D016207:Cytokines