Polarization of PPD-specific T-cell response of patients with tuberculosisfrom Th0 to Th1 profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12

The T helper (Th) 1/Th2 balance in the T-lymphocyte response to purified pr otein derivative (PPD) was evaluated at the clonal level in six Italian and five Gambian patients with pulmonary tuberculosis (TB) before and after an timycobacterial therapy, as well as in five Gambian and four Italian health y immune control subjects. In untreated patients, most PPD-specific clones derived from either peripheral blood or pleural effusions showed a Th0 cyto kine profile (production of both interferon [IFN]-gamma and interleukin [IL ]-4/IL-5). After 6 mo of therapy and clinical healing, most PPD-specific cl ones showed a polarized Th1 profile (production of IFN-gamma but not IL-4/I L-5) in both Italian and Gambian patients. The Th1 polarization was less ma rked in Gambian than in Italian patients and failed to occur in another gro up of four Italian patients who experienced treatment failure. The cytokine profile observed after successful therapy in patients with TB was similar to that found in healthy control subjects, T-cell clones of undefined speci ficity generated from PPD-stimulated cultures showed a similar Th0/Th2 bias in Gambian individuals and Italian patients with treatment failure. The Th 0/Th2-biased responses in Gambian patients before therapy could be modulate d in vitro by IFN-alpha or IL-12, which induced a Th1 polarization of both PPD-specific and bystander T cells. Our data show that active TB associates with a predominant Th0 response to mycobacterial antigens that could play a role in the pathogenesis of the disease. Adjunctive immunotherapy using T h1-polarizing cytokines could increase host defense against mycobacteria an d accelerate healing.