Differential T cell responses to Mycobacterium tuberculosis ESAT6 in tuberculosis patients and healthy donors

Vaccination against and diagnosis of tuberculosis are still insufficient. P roteins secreted by Mycobacterium tuberculosis induce strong immune respons es in tuberculosis and constitute prime candidates for development of novel vaccines against tuberculosis as well as for immunodiagnostic assays. We i nvestigated the role of the secreted proteins MPT63, MPT64 and ESAT6 from M . tuberculosis in healthy individuals and tuberculosis patients. None of th e secreted proteins stimulated peripheral brood mononuclear cells from heal thy donors. In contrast, CD4(+) T cells from many tuberculosis patients wer e stimulated in an MHC class II-restricted fashion by ESAT6, but not by MPT 63 or MPT64. T cell reactivities of tuberculosis patients were focused on t he N-terminal region of ESAT6. The ESAT6 T cell epitopes were presented by different HLA-DR phenotypes. Cell cultures responding to either ESAT6 or sy nthetic peptides thereof showed mRNA transcripts for macrophage inflammator y protein (MIP)-1 alpha, monocyte chemotactic protein (MCP)-1 or IL-8 and p roduction of IFN-gamma and MIP-1 alpha. Our results suggest that the secret ed M. tuberculosis proteins MPT63, MPT64 or ESAT6 do not stimulate unprimed T cells, and that ESAT6 may be a potential candidate antigen for detection of clinical disease.