Contribution of CD8+ T cells to control of Mycobacterium tuberculosis infection.
Tuberculosis is the number one cause of death due to infectious disease in the world today. Understanding the dynamics of the immune response is crucial to elaborating differences between individuals who contain infection vs those who suffer active disease. Key cells in an adaptive immune response to intracellular pathogens include CD8(+) T cells. Once stimulated, these cells provide a number of different effector functions, each aimed at clearing or containing the pathogen. To explore the role of CD8(+) T cells in an integrative way, we synthesize both published and unpublished data to build and test a mathematical model of the immune response to Mycobacterium tuberculosis in the lung. The model is then used to perform a series of simulations mimicking experimental situations. Selective deletion of CD8(+) T cell subsets suggests a differential contribution for CD8(+) T cell effectors that are cytotoxic as compared with those that produce IFN-gamma. We also determined the minimum levels of effector memory cells of each T cell subset (CD4(+) and CD8(+)) in providing effective protection following vaccination.
Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, 48109, USA.
Dhruv
D
Sud
Carolyn
C
Bigbee
Joanne L
JL
Flynn
Denise E
DE
Kirschner
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016753:Interleukin-10 / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*
D016753:Interleukin-10