Treg cells have been implicated in infectious diseases, particularly in chronic or persistent infections 34, 35, but check details discordant results were found ex vivo in terms of Treg expansion during active TB disease, with some authors reporting an increase of CD4+ CD25+FoxP3+ T cells, and other reported the absence of modulation of this T-cell subset 36–40. Moreover, a recent study found that depletion of CD4+ CD25highCD39+ increased M. tuberculosis-specific responses, as well as other recall antigens responses, indicating that Treg broadly modulate antigen-specific immunity 41. In conclusion, this
study shows that active TB disease is associated with an increase in the proportion of 3+ “multifunctional” CD4+ T lymphocytes capable of simultaneously producing IFN-γ, IL-2 and TNF-α, but a relative paucity of CD4+ T cells that produce either both IFN-γ and IL-2, or IFN-γ alone, when compared with the pattern of cytokine produced by CD4+ T cells from LTBI subjects. Strikingly, this pattern of cytokine production seems to be associated with bacterial loads and disease
activity as it reverses 6 months after therapy. These different functional signatures of CD4+ T cells could be used as immunological markers of mycobacterial load to monitor the response to treatment, to evaluate new therapies selleck for active tuberculosis and the efficacy of new vaccines in clinical trials where new biomarkers are needed. Moreover, phenotypic and functional signatures of CD4+ T cells could also be used to monitor individuals LTBI at a high risk of progression to active TB, such as those with HIV coinfection or on anti-TNF therapy. Peripheral blood was obtained from 20 adults with TB disease (11 men, 9 women, age range 46–55 years) from the Dipartimento
di Medicina Clinica e delle Patologie Emergenti, University Hospital, Palermo, and Monaldi Hospital, Naples, Italy, 18 LTBI subjects (10 men, 8 women, age range 38–52 years) and 15 tuberculin (PPD)-negative healthy subjects (8 men and 7 women, age range 41–55 years). Morin Hydrate TB-infected patients had clinical and radiological findings consistent with active pulmonary TB 42. Diagnosis was confirmed by bacteriological isolation of M. tuberculosis in 18 patients. Two further patients were classified as having highly probable pulmonary TB on the basis of clinical and radiological features that were highly suggestive of TB and unlikely to be caused by any other disease; the decision was made by the attending physician to initiate anti-TB chemotherapy, which resulted in an appropriate response to therapy. All patients were treated in accordance with Italian guidelines and received therapy for 6 months. Treatment was successful in all participants all of whom completed the full course of anti-TB chemotherapy, as evidenced by the absence of any clinical or radiographic evidence of recurrent disease and sterile mycobacterial cultures. Peripheral blood was collected before (TB-0) and after completion of chemotherapy (TB-6).