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Impaired degranulation and proliferative capacity of Mycobacterium tuberculosis-specific CD8+ T cells in HIV-infected individuals with latent tuberculosis.

ABSTRACT: Human immunodeficiency virus (HIV)-infected individuals with latent Mycobacterium tuberculosis infection have substantially higher rates of progression to active tuberculosis than HIV-uninfected individuals with latent tuberculosis. To explore HIV-induced deficits in M. tuberculosis-specific CD8+ T-cell functions, we compared interferon ? production, degranulation, and proliferation of CD8+ T cells in response to M. tuberculosis peptides (ESAT-6/CFP-10) between HIV-infected (median CD4+ T-cell count, 522 cells/µL; interquartile range, 318-585 cells/µL) and HIV-uninfected individuals with latent tuberculosis from South Africa. We found that M. tuberculosis-specific degranulation and proliferative capacities were impaired in the HIV-infected group. Thus, our results suggest that HIV coinfection compromises CD8+ T-cell functions in latent tuberculosis.

SUBMITTER: Kalokhe AS

PROVIDER: S-EPMC4351361 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Impaired degranulation and proliferative capacity of Mycobacterium tuberculosis-specific CD8+ T cells in HIV-infected individuals with latent tuberculosis.

Kalokhe Ameeta S AS Adekambi Toidi T Ibegbu Chris C CC Ray Susan M SM Day Cheryl L CL Rengarajan Jyothi J

The Journal of infectious diseases 20140909 4

Human immunodeficiency virus (HIV)-infected individuals with latent Mycobacterium tuberculosis infection have substantially higher rates of progression to active tuberculosis than HIV-uninfected individuals with latent tuberculosis. To explore HIV-induced deficits in M. tuberculosis-specific CD8+ T-cell functions, we compared interferon γ production, degranulation, and proliferation of CD8+ T cells in response to M. tuberculosis peptides (ESAT-6/CFP-10) between HIV-infected (median CD4+ T-cell c ...[more]

PMID: 25205634

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Project description:Containment of Mycobacterium tuberculosis (Mtb) infection requires T cell recognition of infected macrophages. Mtb has evolved to tolerate, evade, and subvert host immunity. Despite a vigorous and sustained CD8+ T cell response during Mtb infection, CD8+ T cells make limited contribution to protection. Here, we ask whether the ability of Mtb-specific T cells to restrict Mtb growth is related to their capacity to recognize Mtb-infected macrophages. We derived CD8+ T cell lines that recognized the Mtb immunodominant epitope TB10.44-11 and compared them to CD4+ T cell lines that recognized Ag85b240-254 or ESAT63-17. While the CD4+ T cells recognized Mtb-infected macrophages and inhibited Mtb growth in vitro, the TB10.4-specific CD8+ T cells neither recognized Mtb-infected macrophages nor restricted Mtb growth. TB10.4-specific CD8+ T cells recognized macrophages infected with Listeria monocytogenes expressing TB10.4. However, over-expression of TB10.4 in Mtb did not confer recognition by TB10.4-specific CD8+ T cells. CD8+ T cells recognized macrophages pulsed with irradiated Mtb, indicating that macrophages can efficiently cross-present the TB10.4 protein and raising the possibility that viable bacilli might suppress cross-presentation. Importantly, polyclonal CD8+ T cells specific for Mtb antigens other than TB10.4 recognized Mtb-infected macrophages in a MHC-restricted manner. As TB10.4 elicits a dominant CD8+ T cell response that poorly recognizes Mtb-infected macrophages, we propose that TB10.4 acts as a decoy antigen. Moreover, it appears that this response overshadows subdominant CD8+ T cell response that can recognize Mtb-infected macrophages. The ability of Mtb to subvert the CD8+ T cell response may explain why CD8+ T cells make a disproportionately small contribution to host defense compared to CD4+ T cells. The selection of Mtb antigens for vaccines has focused on antigens that generate immunodominant responses. We propose that establishing whether vaccine-elicited, Mtb-specific T cells recognize Mtb-infected macrophages could be a useful criterion for preclinical vaccine development.

Dataset Information

Impaired degranulation and proliferative capacity of Mycobacterium tuberculosis-specific CD8+ T cells in HIV-infected individuals with latent tuberculosis.

Publications

Impaired degranulation and proliferative capacity of Mycobacterium tuberculosis-specific CD8+ T cells in HIV-infected individuals with latent tuberculosis.

Similar Datasets

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