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RESEARCH PRODUCT
Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection.
Giuseppe GelsominoAlfredo SalernoSimone A. JoostenAlessandro SanduzziDomenico GalatiFrancesco DieliGiuliana GugginoAlessandro MatareseWilleke P. J. FrankenTom H. M. OttenhoffPaola Di CarloLucina TitoneNadia CaccamoMarialuisa Bocchinosubject
Interleukin 2AdultCD4-Positive T-LymphocytesMaleTuberculosisSettore MED/17 - Malattie InfettiveImmunologyCell SeparationBiologyLymphocyte ActivationFlow cytometryMycobacterium tuberculosis03 medical and health sciences0302 clinical medicineImmune systemBacterial ProteinsCD4(+) T cells Cytokines Mycobacterium tuberculosis infection Tuberculosis disease interferon-gamma immunological memory disease responses protection cytokine immunity bcg vaccination virusmedicineImmunology and AllergyDistribution (pharmacology)HumansCytokineTuberculosis Pulmonary030304 developmental biologyTuberculosis disease.Settore MED/04 - Patologia Generale0303 health sciencesAntigens Bacterialmedicine.diagnostic_testMycobacterium tuberculosis infectionMycobacterium tuberculosisMiddle Agedbiology.organism_classificationmedicine.diseaseFlow CytometryPhenotypeVirologyCD4+ T cellsBacterial Load3. Good healthImmunologyAcute DiseaseChronic DiseaseCytokinesTumor necrosis factor alphaAcyltransferases030215 immunologymedicine.drugdescription
Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametic flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha 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-gamma double and IFN-gamma 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-gamma, IL-2 and TNF-alpha 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-08-31 | European journal of immunology |