Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons

Quiroga, María Florencia; Angerami, Matias; Santucci, Natalia; Ameri, Diego; Francos, José L; Wallach, Jorge C.; Sued, Omar; Cahn, Pedro; Salomón, Horacio

doi:10.1371/journal.pone.0033061

Cited by 18 publications

(32 citation statements)

References 48 publications

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“…Even though a lower number of subjects was analyzed in HIV and HIV-LTB groups, data trends suggest no association between DHEA plasma levels and CD8 + T TE or T TE CD45RA dim proportions in these groups. This lack of association would be in accordance with our previous observation of preserved DHEA levels in these patient groups [19]. No significant correlations were observed between DHEA plasma levels and the percentages of Mtb-specific CD8 + T cells or their effector/memory subsets in any of the groups studied (data not shown).…”

Section: Adrenal Hormones and Their Interrelation With Cd8 + T-cells supporting

confidence: 91%

“…We did not observe any effects of DHEA on CD8 + T-cell responses in those individuals with CD4 + cell counts below 100 cell/μL (data not shown). These results indicate that, as shown previously [19], DHEA exerts its enhancer effect depending on the immune status of the individuals. …”

supporting

confidence: 89%

“…On the contrary, IFN-γ+ T TE originated from T N both in HIV-TB and HD. These analyses show for the first time not only maturation but also cell transition differences depending on cell function during HIV-TB coinfection.Endocrine hormones, and particularly adrenal hormones such as DHEA, are prone to modulate immune functions during HIV-TB coinfection as described previously by our group [19]. According to this, the present study shows that DHEA enhances CD8 + Tcell responses and terminal differentiation ( Fig.…”

supporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

“…In fact, the synthetic DHEA derivative, 16 α-bromoepiandrosterone, exerts beneficial effects in clinical and experimental TB and in HIV patients [16][17][18]. We have previously demonstrated that in vitro treatment of PBMCs from HIV-TB patients with DHEA increased Mtb-specific IFN-γ responses and decreased FoxP3 expression in regulatory T cells, thus inducing a bias toward a protective antitubercular immune response [19].Therefore, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, and effector/memory differentiation of CD8 + T cells during HIV-TB coinfection and their modulation by adrenal hormones, focusing on DHEA effects. Our data show that HIV-TB coinfection is associated with both impaired cytotoxic Mtb-specific CD8 + T-cell responses and irregular CD8 + T-cell differentiation, the latter evidenced by lower CD45RA expression levels in T TE CD8 + T cells and higher PD1 expression restricted to CD27 + CD8 + T cells.…”

mentioning

confidence: 99%

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HIV–TB coinfection impairs CD8⁺ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

et al. 2015

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Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (T TE ) CD8 + T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb).We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8 + T cells, and their modulation by DHEA during HIV-TB coinfection. CD8 + T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and T TE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8 + T cells. Notably, CD8 + T cells from HIV-TB patients displayed higher Terminal Effector (T TE ) CD45RA dim proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8 + T cells from HIV-TB patients increased although restricted to the CD27 + population. Interestingly, DHEA plasma levels positively correlated with T TE in CD8 + T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8 + T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8 + T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8 + T-cell functions during HIV-TB coinfection.Keywords: Coinfection r CD8 + T cells r Cell differentiation r DHEA r HIV r Tuberculosis Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Guadalupe V. Suarez e-mail: suarez_guadalupe@hotmail.com IntroductionNearly one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB). HIV coinfection is the main risk factor for progression C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 2530 Guadalupe V. Suarez et al. Eur. J. Immunol. 2015. 45: 2529-2541 from latent to active TB disease, increasing the risk of latent TB (LTB) reactivation up to 20-fold [1]. It is well established that CD4 + T cells are critical for resistance to Mtb [2]. Mtb infection also elicits CD8 + T-cell responses, which are recruited to the lung during infection and found in the granulomas of infected people [3]. Although it is still unknown how CD8 + T cells may mediate protection against TB, it has been suggested that while CD4 + T cells are more important in controlling bacterial replication during the acute phase of infection, CD8 + T cells play a greater role during latency, possibly via immunesurveillance of cells with higher numbers of intracellular bacilli [4,5]. Besides cytokine secretion (IFN-γ and TNF-α), CD8 + T cells can induce T-cell-mediated cytotoxicity of infected cells, the major function of these cells [6]. Also, cytotoxic CD8 + T cells are able to directly kill intracell...

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Section: Adrenal Hormones and Their Interrelation With Cd8 + T-cells supporting

confidence: 91%

supporting

confidence: 89%

supporting

confidence: 87%