Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo.
Activation of Th1 lymphocytes, IFN-gamma production and macrophage activation are crucial in defense against Mycobacteria. In developing countries, Th2 activation and IL-4 production have been associated in vitro with tuberculosis and with poor clinical outcome after treatment. Serological markers of Th1 [soluble lymphocyte activation gene (LAG)-3] and Th2 (IgE, solubleCD30, and CCL22/macrophage-derived chemokine) activity were measured in 414 HIV-negative tuberculosis patients from The Gambia and Guinée and in 414 healthy household and community controls. Measurements were repeated during treatment to assess the effect of therapy on Th1/Th2 ratio. At diagnosis, sLAG-3 levels were lower in patients than in community controls (p<0.0001), but were higher in household controls exposed to contact with patients than in community controls (p<0.0001). In comparison with community controls, patients had consistently higher levels of IgE, sCD30, and CCL22 (p<0.0001), whereas household controls had lower levels of indicators of Th2 activity (p<0.0001). After treatment, cured patients had higher levels of Th1 (p<0.0001) and lower levels of Th2 (p<0.0001) activity than patients who were not successfully treated or interrupted therapy. In Africa, tuberculosis is associated with low Th1 and high Th2 activity in vivo, whereas close exposure to tuberculosis is associated with a high Th1/Th2 ratio. Patients with favorable outcome after treatment exhibit a higher Th1/Th2 ratio compared to patients with poor clinical outcome.
Medical Research Council Laboratories, Fajara, The Gambia.
Christian
C
Lienhardt
Annalisa
A
Azzurri
Amedeo
A
Amedei
Katherine
K
Fielding
Jackson
J
Sillah
Oumou Y
OY
Sow
Boubacar
B
Bah
Marisa
M
Benagiano
Alimou
A
Diallo
Roberto
R
Manetti
Kebba
K
Manneh
Per
P
Gustafson
Steve
S
Bennett
Mario M
MM
D'Elios
Keith
K
McAdam
Gianfranco
G
Del Prete
D000293:Adolescent; D000328:Adult; D000349:Africa; D000368:Aged; D015703:Antigens, CD; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000032:analysis; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D017730:Ki-1 Antigen / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; C515482:CCL22 protein, human; D054422:Chemokine CCL22; D019742:Chemokines, CC; D017730:Ki-1 Antigen; D008565:Membrane Proteins; D007073:Immunoglobulin E; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human; C000720328:soluble LAG-3 protein, human