Defining the contribution of T cell exhaustion to failed immunity during TB
| Autor: | Miye K Jacques, Pushpa Jayaraman, Vijay K Kuchroo, Samuel M Behar |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 196:65.17-65.17 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Tuberculosis is a pulmonary disease, caused by Mycobacterium tuberculosis (Mtb) infection, which affects approximately one third of the global population and is a major public health concern. Although T cells are essential in mediating protection against Mtb infection, they are often unable to sterilize infected tissues. One possible reason for an ineffective immune response is the onset of T cell exhaustion or dysfunction. T cell exhaustion is characterized by the progressive loss of T cell effector function accompanied by an increase in expression of inhibitory receptors. Here we show that during Mtb infection, T cells express the inhibitory molecules Tim3 and PD1, and T cells that express both Tim3 and PD1 have decreased IFNγ and TNF production. In addition, antibody blockade of Tim3 improves T cell function and decreases bacterial burden. These results indicate that T cells are functionally exhausted during chronic Mtb infection and that blockade of inhibitory receptors can re-invigorate T cell function and improve the outcome of infection. Based on a possible role for CEACAM1 in the T cell inhibitory signal mediated by Tim3, we are currently performing experiments to determine how CEACAM1 affects host defense against Mtb. Understanding the roles of inhibitory receptors, such as Tim3 and PD1, during Mtb infection is providing insight into why T cell immunity is insufficient to eradicate Mtb infection. |
| Databáze: | OpenAIRE |
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