Immune biology of macaque lymphocyte populations during mycobacterial infection.
Immune responses of lymphocyte populations during early phases of mycobacterial infection and reinfection have not been well characterized in humans. A non-human primate model of Mycobacterium bovis bacille Calmette-Guerin (BCG) infection was employed to characterize optimally the immune responses of mycobacteria-specific T cells. Primary BCG infection induced biphasic immune responses, characterized by initial lymphocytopenia and subsequent expansion of CD4+, CD8+ and gammadelta T cell populations in the blood, lymph nodes and the pulmonary compartment. The potency of detectable T cell immune responses appears to be influenced by the timing and route of infection as well as challenge doses of BCG organisms. Systemic BCG infection introduced by intravenous challenge induced a dose-dependent expansion of circulating CD4+, CD8+ and gammadelta T cells whereas, in the pulmonary compartment, the systemic infection resulted in a predominant increase in numbers of gammadelta T cells. In contrast, pulmonary exposure to BCG through the bronchial route induced detectable expansions of CD4+, CD8+ and gammadelta T cell populations in only the lung but not in the blood. A rapid recall expansion of these T cell populations was seen in the macaques reinfected intravenously and bronchially with BCG. The expanded alphabeta and gammadelta T cell populations exhibited their antigen specificity for mycobacterial peptides and non-peptide phospholigands, respectively. Finally, the major expansion of T cells was associated with a resolution of active BCG infection and reinfection. The patterns and kinetics of CD4+, CD8+ and gammadelta T cell immune responses during BCG infection might contribute to characterizing immune protection against tuberculosis and testing new tuberculosis vaccines in primates.
Lai
X
X
Tuberculosis Research Unit, Beth Israel Deaconess, Medical Center, Harvard Medical School, Boston, MA, USA.
Shen
Y
Y
Zhou
D
D
Sehgal
P
P
Shen
L
L
Simon
M
M
Qiu
L
L
Letvin
N L
NL
Chen
Z W
ZW
D000818:Animals; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology / Q000382:microbiology; D008253:Macaca mulatta; D008254:Macaca nemestrina; D009164:Mycobacterium Infections / Q000276:immunology*; D009163:Mycobacterium bovis; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000276:immunology*