The influence of age on the cellular immune response in patients with tuberculosis and healthy controls

[摘要] ENGLISH ABSTRACT:Children and adults may differ in their immune function. An adequate function of theindividual's immune system is crucial to the risk for development of tuberculosis (TB)after infection with Mycobacterium tuberculosis (Mtb). Epidemiological evidencesuggests an age-related incidence of TB. Furthermore, the prevailing clinical expressiont 'of TB varies between age groups.-The aims of this study were to characterise the cellular immune response at different agesin TB patients and healthy individuals living in a region highly endemic for TB and torelate the findings to the clinical expression of TB in different age groups.A total of 150 persons of different ages were included in this study: 50 TB patients,(identified on the basis of clinical, radiological and microbiological characteristics), 49healthy Mantoux positive (~15mm) and 51 healthy Mantoux negative (<15mm) subjects.All patients <12yrs were identified as having primary TB and postprimary TB was onlydiagnosed in patients ~12yrs.Haematologic indices were obtained from all the included subjects and found to be agerelated.With the exception of the absolute lymphocyte counts, all indices weresignificantly different in TB patients when compared to healthy controls.Whole blood was cultured and stimulated with PHA, PPD and ESAT -6 to measurelymphocyte proliferation and IFN-y, TNF-a, IL-2 and IL-10 production in thesupernatants of the cultures.After stimulation with PHA, the production of IFN-y, TNF-a and IL-10 as well aslymphocyte proliferation were all age-related.After stimulation with PPD, age correlated positively with IFN-y production in healthyMantoux positive subjects< 12yrs. In the age groups <20 yrs, patients produced similar amounts of IFN-y when compared to healthy age-related Mantoux positive controls.TNF-a and IL-2 production were not different between patients and controls. In thiswhole blood system, measuring any of these cytokines on their own did not differentiatepatients from controls at all ages.The ratio of PPD stimulated IFN-y to TNF-a production was significantly less in patientswith primary TB and postprimary TB when compared to Mantoux positive controls,irrespective of age. These findings indicate that calculated ratios between severalcytokines may be useful markers of disease at all ages.ESA T -6 stimulated IFN -y production did not result in any significant correlation withage, but was significantly less in healthy Mantoux positive subjects ~12 yrs whencompared to healthy Mantoux positive subjects <12 yrs and TB patients of all ages. Thisfinding suggests that a positive immune response to ESAT -6 is indicative of recentimmunological contact with Mtb.Total IgE was measured in serum. In children <12 yrs these values correlated with ageand were highest in healthy Mantoux positive controls, thereby not confirming anyinverse correlation between IgE and TB.Age should be recognised as a significant variable in quantitative measurements ofcellular immune responses.

[发布机构] Stellenbosch University