Initiation and regulation of T-cell responses in tuberculosis

Abstract

Tuberculosis (TB) poses a great challenge to immunologists, as it represents a chronic infection characterized by persistence of the pathogen despite development of antigen-specific immune responses. Among the characteristics of adaptive immune responses to Mycobacterium tuberculosis is a delay in the onset of detectable T-cell responses, in both humans and experimental animals. Recent studies have revealed mechanisms that contribute to this delay, including pathogen inhibition of apoptosis, delayed migration of dendritic cells from the lungs to the local lymph node, and influence of regulatory T cells. In addition, novel features of M. tuberculosis antigen-specific T-cell differentiation have been discovered, which reveal pathways that limit and promote immune control of infection. Taken together, these results highlight the need for additional basic research and provide optimism for the development of TB vaccines with greater efficacy.

Figure 1

Delayed onset of adaptive immunity in tuberculosis compared with other infections. In acute, resolving infections, T-cell responses are initiated 3–5 days after initial infection; they peak 7–8 days after infection, and subsequently contract to establish memory populations. After aerosol infection with M. tuberculosis, T-cell responses are not initiated until 9–11 days after infection, peak several weeks after infection, and bacteria are not eliminated. LCMV, lymphocytic choriomeningitis virus.