Th0 to Th1 switch of CD4 T cell clones specific from the 16-kDa antigen of Mycobacterium tuberculosis after successful therapy: lack of involvement of epitope repertoire and HLA-DR

Abstract

In this study, we have examined the influence of HLA-DR molecules and the structure of the epitope repertoire of the 16-kDa protein of Mycobacterium tuberculosis on the acquisition of the cytokine secretion pattern of CD4 T cell clones, obtained from tuberculous patients before and after anti-mycobacterial therapy. Our data indicate that TB patients have a predominant Th0 response against the 16-kDa protein and its epitopes and that healing, induced by anti-mycobacterial therapy, is associated with a shift toward a predominant Th1 phenotype. Moreover, both HLA-DR molecules restricting the clone specificity and the nature of the recognized epitope do not play any role in the generation of Th0 and Th1 clones. These findings indicate that additional factors, such as the cytokine environment and/or costimulatory molecules, determine the Th phenotype of CD4 T cells during tuberculosis.