Abstract
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.
Highlights
Tuberculosis (TB) is the deadliest infectious disease worldwide, even if the global incidence has declined over the past decades
In M. tuberculosis infection, the role of Natural killer T (NKT) cell subsets has been investigated; here, we report some evidences of their role depending on the type of mycobacterial antigens recognized
Similar to helper CD4 T cells, notwithstanding their specificity for α-galactosyl ceramide (αGalCer) recognition, they are able to produce different cytokines such as interferon γ (IFN-γ), interleukin 4 (IL4), or IL-17A, which designate them as iNKT1, iNKT2, and iNKT17
Summary
Host-directed immunotherapies could offer therapeutic strategies for patients with drug-resistant TB or with HIV and TB coinfection. 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, MHCrelated protein-1–restricted mucosal-associated invariant T (MAIT) cells, MHC class Ib–reactive T cells, and γδ T cells.
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