| Summary: | Even if the incidence of tuberculosis (TB) has been decreasing over the last years, the number of patients with TB is increasing worldwide. The emergence of multidrug-resistant and extensively drug-resistant TB is making control of TB more difficult. Mycobacterium bovis bacillus Calmette–Guérin vaccine fails to prevent pulmonary TB in adults, and there is an urgent need for a vaccine that is also effective in patients with human immunodeficiency virus (HIV) coinfection. Therefore, TB control may benefit on novel therapeutic options beyond antimicrobial treatment. Host-directed immunotherapies could offer therapeutic strategies for patients with drug-resistant TB or with HIV and TB coinfection. In the last years, the use of donor lymphocytes after hematopoietic stem cell transplantation has emerged as a new strategy in the cure of hematologic malignancies in order to induce graft-versus leukemia and graft-versus-infection effects. Moreover, adoptive therapy has proven to be effective in controlling cytomegalovirus and Epstein-Barr virus reactivation in immunocompromised patients with ex vivo expanded viral antigen-specific T cells. Unconventional T cells are a heterogeneous group of T lymphocytes with limited diversity. One of their characteristics is that antigen recognition is not restricted by the classical major histocompatibility complex (MHC). They include CD1 (cluster of differentiation 1)–restricted T cells, MHC-related protein-1–restricted mucosal-associated invariant T (MAIT) cells, MHC class Ib–reactive T cells, and γδ T cells. Because these T cells are genotype-independent, they are also termed “donor unrestricted” T cells. The combined features of low donor diversity and the lack of genetic restriction make these cells suitable candidates for T cell–based immunotherapy of TB.
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