Cytolytic CD8+ T Cells Recognizing CFP10 Are Recruited to the Lung after Mycobacterium tuberculosis Infection

Optimum immunity against Mycobacterium tuberculosis requires both CD4+ and CD8+ T cells. In contrast with CD4+ T cells, few antigens are known that elicit CD8+ T cells during infection. CD8+ T cells specific for culture filtrate protein-10 (CFP10) are found in purified protein derivative positive donors, suggesting that CFP10 primes CD8+ T cells in vivo. Using T cells from M. tuberculosis–infected mice, we identified CFP10 epitopes recognized by CD8+ T cells and CD4+ T cells. CFP10-specific T cells were detected as early as week 3 after infection and at their peak accounted for up to 30% of CD8+ T cells in the lung. IFNγ-producing CD8+ and CD4+ T cells recognizing CFP10 epitopes were preferentially recruited to the lungs of M. tuberculosis–infected mice. In vivo cytolytic activity of CD8+ T cells specific for CFP10 and TB10.3/10.4 proteins was detected in the spleen, pulmonary lymph nodes, and lungs of infected mice. The cytolytic activity persisted long term and could be detected 260 d after infection. This paper highlights the cytolytic function of antigen-specific CD8+ T cells elicited by M. tuberculosis infection and demonstrates that large numbers of CFP10-specific cytolytic CD8+ T cells are recruited to the lung after M. tuberculosis infection

Anamnestic Responses of Mice following Mycobacterium tuberculosis Infection

The anamnestic response is the property of the immune system that makes vaccine development possible. Although the development of a vaccine against Mycobacterium tuberculosis is an important global priority, there are many gaps in our understanding of how immunological memory develops following M. tuberculosis infection or after BCG vaccination. In experiments designed to compare the anamnestic response of susceptible and resistant mouse strains, major histocompatibility complex-matched memory-immune C3.SW-H2(b)/SnJ and C57BL/6 mice both demonstrated better control of bacterial replication following reinfection with M. tuberculosis than control mice. Nevertheless, this memory response did not appear to have any long-term protective effect for either mouse strain. A greater understanding of the immunological factors that govern the maintenance of immunological memory following exposure to M. tuberculosis will be required to develop an effective vaccine

Toll-Like Receptor 4-Defective C3H/HeJ Mice Are Not More Susceptible than Other C3H Substrains to Infection with Mycobacterium tuberculosis

Mycobacterium tuberculosis produces a variety of molecules capable of activating Toll-like receptors, a family of pattern recognition receptors expressed by macrophages and a variety of other cells. To determine whether Toll-like receptor 4 (TLR4) was critical in resistance to M. tuberculosis infection, we compared the morbidity and mortality of TLR4-defective C3H/HeJ mice to those of TLR4-sufficient C3H mouse substrains. TLR4-defective C3H/HeJ mice and TLR4-sufficient C3H/HeSnJ, C3HeB/FeJ, and C3H/HeOuJ mice were infected by the aerosol route with M. tuberculosis. TLR4-defective C3H/HeJ mice had levels of cytokines in their bronchoalveolar lavage fluids and in vitro mycobacterial antigen-specific recall responses similar to those of other C3H mouse substrains. In addition, bacterial replication and long-term survival of mice following infection appeared to be independent of TLR4. Interestingly, C3HeB/FeJ mice were significantly more susceptible to M. tuberculosis infection, indicating that genetic heterogeneity among inbred C3H mouse substrains modifies resistance to infection. Therefore, cautious interpretation is required when the C3H/HeJ strain is used as a model of a TLR4-defective mouse strain, as there are significant allelic differences between C3H/HeJ and other C3H mouse substrains in response to M. tuberculosis infection. With this caveat, our data indicate that TLR4 may not be required for optimal immunity of mice to M. tuberculosis