| First Author | Jayaraman P | Year | 2016 |
| Journal | PLoS Pathog | Volume | 12 |
| Issue | 3 | Pages | e1005490 |
| PubMed ID | 26967901 | Mgi Jnum | J:247337 |
| Mgi Id | MGI:5916345 | Doi | 10.1371/journal.ppat.1005490 |
| Citation | Jayaraman P, et al. (2016) TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection. PLoS Pathog 12(3):e1005490 |
| abstractText | While T cell immunity initially limits Mycobacterium tuberculosis infection, why T cell immunity fails to sterilize the infection and allows recrudescence is not clear. One hypothesis is that T cell exhaustion impairs immunity and is detrimental to the outcome of M. tuberculosis infection. Here we provide functional evidence for the development T cell exhaustion during chronic TB. Second, we evaluate the role of the inhibitory receptor T cell immunoglobulin and mucin domain-containing-3 (TIM3) during chronic M. tuberculosis infection. We find that TIM3 expressing T cells accumulate during chronic infection, co-express other inhibitory receptors including PD1, produce less IL-2 and TNF but more IL-10, and are functionally exhausted. Finally, we show that TIM3 blockade restores T cell function and improves bacterial control, particularly in chronically infected susceptible mice. These data show that T cell immunity is suboptimal during chronic M. tuberculosis infection due to T cell exhaustion. Moreover, in chronically infected mice, treatment with anti-TIM3 mAb is an effective therapeutic strategy against tuberculosis. |
