A decrease in PPD specific CD4 T cell CD38 and HLA-DR expression in pulmonary tuberculosis patients after 8 weeks of therapy correlates with successful anti-tuberculosis treatment

Abstract

Tuberculosis (TB) is a major health problem in Indonesia with a million new cases each year. The CD4 T cell adaptive immune response against Mycobacterium tuberculosis (MTB) is central to the control of this disease. We investigated whether standard therapy of TB causes changes to these cells in the early stages of treatment. To do this we took blood samples from 2 groups of TB patients in Banda Aceh, Indonesia; one from a group of patients before treatment, and the other from a group who become smear negative after 8 weeks treatment. MTB specific CD4 T cells were identified by ex vivo stimulation with PPD and flow cytometric measurement of intracellular cytokines and surface markers. We found no difference in total PPD specific CD4 T cells between the groups, but that the proportion of these cells CD38 + HLA-DR+ was significantly lower in the treatment group. This decrease was not specific to Interferon gamma (IFNg), Interleukin-2 (IL-2) or Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) producing cells. Our findings show that anti-MTB treatment affects the adaptive immune response, and that measuring the decrease of the PPD specific CD4 T cell CD38+HLA-DR+ phenotype could be a useful parameter for determination of treatment success.