Polyfunctional CD4+ T Cells As Targets for Tuberculosis Vaccination
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of morbidity and mortality worldwide, despite the widespread use of the only licensed vaccine, Bacille Calmette Guerin (BCG). Eradication of TB will require a more effective vaccine, yet evaluation of new vaccine...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01262/full |
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| author | Deborah A. Lewinsohn David M. Lewinsohn David M. Lewinsohn Thomas J. Scriba |
| author_facet | Deborah A. Lewinsohn David M. Lewinsohn David M. Lewinsohn Thomas J. Scriba |
| author_sort | Deborah A. Lewinsohn |
| collection | DOAJ |
| description | Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of morbidity and mortality worldwide, despite the widespread use of the only licensed vaccine, Bacille Calmette Guerin (BCG). Eradication of TB will require a more effective vaccine, yet evaluation of new vaccine candidates is hampered by lack of defined correlates of protection. Animal and human studies of intracellular pathogens have extensively evaluated polyfunctional CD4+ T cells producing multiple pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) as a possible correlate of protection from infection and disease. In this study, we review the published literature that evaluates whether or not BCG and/or novel TB vaccine candidates induce polyfunctional CD4+ T cells and if these T cell responses correlate with vaccine-mediated protection. Ample evidence suggests that BCG and several novel vaccine candidates evaluated in animal models and humans induce polyfunctional CD4+ T cells. However, while a number of studies utilizing the mouse TB model support that polyfunctional CD4+ T cells are associated with vaccine-induced protection, other studies in mouse and human infants demonstrate no correlation between these T cell responses and protection. We conclude that induction of polyfunctional CD4+ T cells is certainly not sufficient and may not even be necessary to mediate protection and suggest that other functional attributes, such as additional effector functions, T cell differentiation state, tissue homing potential, or long-term survival capacity of the T cell may be equally or more important to promote protection. Thus, a correlate of protection for TB vaccine development remains elusive. Future studies should address polyfunctional CD4+ T cells within the context of more comprehensive immunological signatures of protection that include other functions and phenotypes of T cells as well as the full spectrum of immune cells and mediators that participate in the immune response against Mtb. |
| first_indexed | 2024-12-21T06:16:45Z |
| format | Article |
| id | doaj.art-643a3cdba6854368a3badec87837ff57 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T06:16:45Z |
| publishDate | 2017-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-643a3cdba6854368a3badec87837ff572022-12-21T19:13:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01262295382Polyfunctional CD4+ T Cells As Targets for Tuberculosis VaccinationDeborah A. Lewinsohn0David M. Lewinsohn1David M. Lewinsohn2Thomas J. Scriba3Division of Infectious Disease, Department of Pediatrics, Oregon Health and Science University, Portland, OR, United StatesPulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, OR, United StatesDepartment of Medicine, VA Portland Health Care System, Portland, OR, United StatesSouth African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South AfricaTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of morbidity and mortality worldwide, despite the widespread use of the only licensed vaccine, Bacille Calmette Guerin (BCG). Eradication of TB will require a more effective vaccine, yet evaluation of new vaccine candidates is hampered by lack of defined correlates of protection. Animal and human studies of intracellular pathogens have extensively evaluated polyfunctional CD4+ T cells producing multiple pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) as a possible correlate of protection from infection and disease. In this study, we review the published literature that evaluates whether or not BCG and/or novel TB vaccine candidates induce polyfunctional CD4+ T cells and if these T cell responses correlate with vaccine-mediated protection. Ample evidence suggests that BCG and several novel vaccine candidates evaluated in animal models and humans induce polyfunctional CD4+ T cells. However, while a number of studies utilizing the mouse TB model support that polyfunctional CD4+ T cells are associated with vaccine-induced protection, other studies in mouse and human infants demonstrate no correlation between these T cell responses and protection. We conclude that induction of polyfunctional CD4+ T cells is certainly not sufficient and may not even be necessary to mediate protection and suggest that other functional attributes, such as additional effector functions, T cell differentiation state, tissue homing potential, or long-term survival capacity of the T cell may be equally or more important to promote protection. Thus, a correlate of protection for TB vaccine development remains elusive. Future studies should address polyfunctional CD4+ T cells within the context of more comprehensive immunological signatures of protection that include other functions and phenotypes of T cells as well as the full spectrum of immune cells and mediators that participate in the immune response against Mtb.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01262/fullT-cell immunityCD4+ T cellsvaccine-induced immunitytuberculosisvaccineprotective immunity |
| spellingShingle | Deborah A. Lewinsohn David M. Lewinsohn David M. Lewinsohn Thomas J. Scriba Polyfunctional CD4+ T Cells As Targets for Tuberculosis Vaccination Frontiers in Immunology T-cell immunity CD4+ T cells vaccine-induced immunity tuberculosis vaccine protective immunity |
| title | Polyfunctional CD4+ T Cells As Targets for Tuberculosis Vaccination |
| title_full | Polyfunctional CD4+ T Cells As Targets for Tuberculosis Vaccination |
| title_fullStr | Polyfunctional CD4+ T Cells As Targets for Tuberculosis Vaccination |
| title_full_unstemmed | Polyfunctional CD4+ T Cells As Targets for Tuberculosis Vaccination |
| title_short | Polyfunctional CD4+ T Cells As Targets for Tuberculosis Vaccination |
| title_sort | polyfunctional cd4 t cells as targets for tuberculosis vaccination |
| topic | T-cell immunity CD4+ T cells vaccine-induced immunity tuberculosis vaccine protective immunity |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01262/full |
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