High resolution radiographic and fine immunologic definition of TB disease progression in the rhesus macaque.
Mycobacterium tuberculosis infection in non-human primates parallels human tuberculosis, and provides a valuable vaccine evaluation model. However, this model is limited by the availability of real-time, non-invasive information regarding disease progression. Consequently, we have combined computed tomography scanning with enumeration of antigen-specific T cell responses. Four rhesus monkeys were infected with M. tuberculosis strain H37Rv (1000 cfu) in the right lower lobe via a bronchoscope. All uniformly developed progressive tuberculosis, and required euthanasia at 12 weeks. Computed tomography scanning provided detailed real-time imaging of disease progression. At necropsy, computed tomography and pathohistologic findings were tightly correlated, and characteristic of human disease. Immunologic monitoring demonstrated progressive evolution of high frequency M. tuberculosis-specific CD4(+) and CD8(+) T cell responses. Peripheral blood effector cell frequencies were similar to those observed in tissues. In summary, computed tomography scanning in conjunction with immunologic monitoring provides a non-invasive, accurate, and rapid assessment of tuberculosis in the non-human primate.
Lewinsohn
David M
DM
Pulmonary & CCM, R&D 11, Portland VA Medical Center, 3710 SW US Veterans Road, Portland, OR 97239, USA. lewinsod@ohsu.edu <lewinsod@ohsu.edu>
Tydeman
Ian S
IS
Frieder
Marisa
M
Grotzke
Jeff E
JE
Lines
Rebecca A
RA
Ahmed
Sheela
S
Prongay
Kamm D
KD
Primack
Steven L
SL
Colgin
Lois M A
LM
Lewis
Anne D
AD
Lewinsohn
Deborah A
DA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D006651:Histocytochemistry; D008168:Lung / Q000000981:diagnostic imaging* / Q000382:microbiology / Q000473:pathology; D008253:Macaca mulatta; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D014057:Tomography, X-Ray Computed; D014376:Tuberculosis / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology