Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection.
Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-γ/IL-2/TNF-α triple expressors, IFN-γ/IL-2, IFN-γ/TNF-α or TNF-α/IL-2 double expressors or IFN-γ, IL-2 or TNF-α single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-γ double and IFN-γ single expressors as compared with the other CD4(+) T-cell subsets. Proportions of the other double or single CD4(+) T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-γ, IL-2 and TNF-α profiles of M. tuberculosis-specific CD4(+) T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4(+) T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy.
Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, University of Palermo, Palermo, Italy.
Nadia
N
Caccamo
Giuliana
G
Guggino
Simone A
SA
Joosten
Giuseppe
G
Gelsomino
Paola
P
Di Carlo
Lucina
L
Titone
Domenico
D
Galati
Marialuisa
M
Bocchino
Alessandro
A
Matarese
Alfredo
A
Salerno
Alessandro
A
Sanduzzi
Willeke P J
WP
Franken
Tom H M
TH
Ottenhoff
Francesco
F
Dieli
D000208:Acute Disease; D000217:Acyltransferases / Q000276:immunology; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D058491:Bacterial Load / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D002469:Cell Separation; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C525005:ESAT-6 antigen, Mycobacterium leprae; C072681:Mycobacterium tuberculosis antigens; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis