TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection

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. © 2016 jayaraman et al.