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Characterization of Mycobacterium tuberculosis–Specific Cells Using MHC Class II Tetramers Reveals Phenotypic Differences Related to HIV Infection and Tuberculosis Disease
| Content Provider | Scilit |
|---|---|
| Author | Strickland, Natalie Müller, Tracey L. Berkowitz, Natacha Goliath, Rene Carrington, Mary N. Wilkinson, Robert J. Burgers, Wendy A. Riou, Catherine |
| Copyright Year | 2017 |
| Description | A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective $CD4^{+}$ T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis–specific $CD4^{+}$ T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M. tuberculosis–specific MHC class II tetramers. We examined the phenotype as well as function of ex vivo M. tuberculosis–specific $tetramer^{+}CD4^{+}$ T cells using flow cytometry. The numbers of M. tuberculosis–specific $tetramer^{+}CD4^{+}$ T cells were relatively well maintained in HIV-infected persons with aTB, despite severe immunodeficiency. However, although HIV-uninfected persons with latent TB infection exhibited ex vivo M. tuberculosis–specific $CD4^{+}$ T cells predominantly of a $CXCR3^{+}CCR6^{+}CCR4^{−}$ (Th1*) phenotype, aTB or HIV infection was associated with a contraction of this subset. Nevertheless, in individuals with aTB and/or HIV infection, circulating ex vivo M. tuberculosis–specific $CD4^{+}$ T cells did not display defects in exhaustion or polyfunctionality compared with healthy HIV-uninfected individuals with latent TB infection. Collectively, these data suggest that increased susceptibility to TB disease could be related to a loss of circulating Th1* $CD4^{+}$ T cells rather than major changes in the number or function of circulating $CD4^{+}$ T cells. |
| Ending Page | 2450 |
| Page Count | 11 |
| Starting Page | 2440 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1700849 |
| Journal | The Journal of Immunology |
| Issue Number | 7 |
| Volume Number | 199 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2017-10-01 |
| Access Restriction | Open |
| Subject Keyword | Mycobacterium Tuberculosis Latent Tuberculosis Infection Active Tuberculosis Mhc Class Ii Tetramers Mtb-specific Cd4+ T Cells Ex Vivo Phenotype |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
