A novel nonclassic beta2-microglobulin-restricted mechanism influencing early lymphocyte accumulation and subsequent resistance to tuberculosis in the lung.
In this study, we compared the course of a low-dose aerosol Mycobacterium tuberculosis infection in mice bearing gene disruptions for the beta2-microglobulin molecule, the CD8 molecule, and the CD1 molecule. Over the first 50 d of infection, the CD8- and CD1-disrupted mice were no more susceptible to infection than were the control mice. In contrast, the bacterial load in beta2-microglobulin gene-disrupted mice increased rapidly and attained much higher levels than that observed in the other gene-disrupted mice and in control mice. A second major difference between the beta2-microglobulin gene-disrupted mice and the other animals was the development of lung granulomas; both the CD8- and CD1-disrupted mice developed essentially normal granulomas except for an apparent increased lymphocyte influx in the CD8-disrupted mice. The beta2-microglobulin gene-disrupted mice, on the other hand, developed granulomas virtually devoid of lymphocytes, with these cells instead localized within prominent perivascular cuffing adjacent to the lesions. These data support the hypothesis that a beta2-microglobulin-dependent, non-CD8- and non-CD1-dependent mechanism controls the early and efficient influx of protective lymphocytes into infected lesions, and that the absence of this mechanism decreases the capacity of the animal to initially deal with pulmonary tuberculosis.
Mycobacterial Research Laboratories, Departments of Microbiology and Pathology, Colorado State University, Fort Collins, Colorado 80523, USA.
C D
CD
D'Souza
A M
AM
Cooper
A A
AA
Frank
S
S
Ehlers
J
J
Turner
A
A
Bendelac
I M
IM
Orme
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000502:physiology*
D018949:Antigens, CD1; D016827:CD8 Antigens; D018932:Chemokine CCL2; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D007371:Interferon-gamma