Phenotyping of circulating CD8+ T cell subsets in human cutaneous leishmaniasis

Khamesipour, Ali; Rostami, Mahmoud Nateghi; Tasbihi, Minoo; Shahrestani, Tahereh; Sarrafnejad, Abdolfattah; Sohrabi, Yahya; Eskandari, Seyed Ebrahim; Valian, Hossein Keshavarz

doi:10.1016/j.micinf.2012.02.006

Cited by 22 publications

(25 citation statements)

References 45 publications

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“…Some studies indicate that cytokine production is dependent on the kind of T-cell subset involved and that naive T cells can also produce the IFN-␥ and TNF-␣ cytokines but at a lower level than T CM and T EM (16)(17)(18)28). In this study, Th1 cytokines in the CD4 ϩ or CD8 ϩ CFSE dim T cells were produced mainly by the T CM and T EM memory subsets.…”

Section: Stimulated Cd8mentioning

confidence: 46%

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Rond

Schure

Öztürk

et al. 2015

Clin. Vaccine Immunol.

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dWhooping cough remains a problem despite vaccination, and worldwide resurgence of pertussis is evident. Since cellular immunity plays a role in long-term protection against pertussis, we studied pertussis-specific T-cell responses. Around the time of the preschool acellular pertussis (aP) booster dose at 4 years of age, T-cell memory responses were compared in children who were primed during infancy with either a whole-cell pertussis (wP) or an aP vaccine. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with pertussis vaccine antigens for 5 days. T cells were characterized by flow-based analysis of carboxyfluorescein succinimidyl ester (CFSE) dilution and CD4, CD3, CD45RA, CCR7, gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣) expression. Before the aP preschool booster vaccination, both the proliferated pertussis toxin (PT)-specific CD4؉ and CD8 ؉ T-cell fractions (CFSE dim ) were higher in aP-than in wP-primed children. Post-booster vaccination, more pertussis-specific CD4؉ effector memory cells (CD45RA ؊ CCR7 ؊ ) were induced in aP-primed children than in those primed with wP. The booster vaccination did not appear to significantly affect the T-cell memory subsets and functionality in aP-primed or wP-primed children. Although the percentages of Th1 cytokine-producing cells were alike in aP-and wP-primed children pre-booster vaccination, aP-primed children produced more Th1 cytokines due to higher numbers of proliferated pertussis-specific effector memory cells. At present, infant vaccinations with four aP vaccines in the first year of life result in pertussis-specific CD4 ؉ and CD8 ؉ effector memory T-cell responses that persist in children until 4 years of age and are higher than those in wP-primed children. The booster at 4 years of age is therefore questionable; this may be postponed to 6 years of age.

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Section: Stimulated Cd8mentioning

confidence: 46%

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Rond

Schure

Öztürk

et al. 2015

Clin. Vaccine Immunol.

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“…We analyzed bulk CD8 + T-cell differentiation based on the expression of CD27 and CD45RA surface proteins as depicted in Fig. 1 [20][21][22][23]. HIV-infected patients with active TB (HIV-TB) or latent TB (HIV-LTB) and HIV + patients with no Mtb coinfection (HIV + ) displayed different subset distributions in total peripheral CD8 + T cells compared to healthy donors (HD) (Fig.…”

Section: Resultsmentioning

confidence: 99%

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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“…CD8 ϩ T cells were isolated from 1 ϫ 10 7 PBMC/ml by use of a magnetic bead sorting system and a monoclonal anti-CD8 antibody according to the manufacturer's instructions (Dynabeads untouched human CD8 T cells; Invitrogen Dynal AS, Oslo, Norway). Monocytes (MOs) were isolated from 5 ϫ 10 6 PBMC/ml by use of magnetic beads (Dynabeads untouched human monocytes; Invitrogen Dynal AS, Oslo, Norway) as previously described (22). The process was performed twice, and these cells were washed with phosphate-buffered saline (PBS) and adjusted to a concentration of 1 ϫ 10 6 MOs/ml in complete RPMI medium.…”

Section: Methodsmentioning

confidence: 99%

Protective and Pathological Functions of CD8⁺T Cells in Leishmania braziliensis Infection

et al. 2015

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dCutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a strong Th1 response that leads to skin lesion development. In areas where L. braziliensis transmission is endemic, up to 15% of healthy subjects have tested positive for delayed-type hypersensitivity to soluble leishmania antigen (SLA) and are considered to have subclinical (SC) infection. SC subjects produce less gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) than do CL patients, but they are able to control the infection. ؉ T cells was higher in CL than in SC cells. While the use of a granzyme B inhibitor decreased the number of apoptotic cells in the CL group, the use of z-VAD-FMK had no effect on the frequency of these cells. These results suggest that CL CD8 ؉ T cells are more cytotoxic and may be involved in pathology. L eishmaniasis is caused by infection with parasites of the genusLeishmania. Leishmaniasis is a neglected tropical disease; 214,000 new cases of cutaneous leishmaniasis (CL) are reported annually worldwide, and the estimated incidence of leishmaniasis is 690,000 to 1,200,000 cases. Approximately 67,000 cases are reported in South America, Central America, and the Caribbean (1). In mice, the majority of Leishmania-specific CD4 ϩ T cells differentiate into T-helper 1 (Th1) cells that secrete gamma interferon (IFN-␥) and contribute to the elimination of the parasite through the activation of macrophages (2, 3). Although protective immunity has predominantly been related to IFN-␥-producing CD4 ϩ T cells, infection with Leishmania also results in the activation and expansion of parasite-specific CD8 ϩ T cells (4, 5). Human CL caused by Leishmania braziliensis is characterized by a strong Th1 response with the production of high levels of IFN-␥ and tumor necrosis factor alpha (TNF-␣) (6, 7). This exaggerated Th1 response is associated with the development of lesions and the severity of the disease (6, 8-10). In patients with CL caused by L. braziliensis, there are more CD4 ϩ than CD8 ϩ T cells, but this ratio reaches an equilibrium due to the increase in CD8 ϩ T cells that occurs during the healing process (11). The enrichment of Leishmania-reactive CD8 ϩ T cells in older lesions suggests that these cells may play a role in the healing process (12). In contrast, other studies have associated CD8ϩ T cell functions with pathology. For example, the cytotoxicity mediated by CD8 ϩ T cells is greater in mucosal leishmaniasis (ML), a more severe form of L. braziliensis infection, than in CL (13,14). More recently, it was shown that the frequency with which CD8 ϩ T cells express granzyme in the lesions of CL patients is greater than that in patients in the early phase of CL (i.e., before the ulcer has developed) and that the frequency with which CD8 ϩ T cells express granzyme is directly associated with the intensity of the inflammatory reaction observed in CL ulcers (15,16). This controversy regarding the role of cytotoxicity in the pathogenesis of human leishmaniasis indicates that the functions of CD...

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Phenotyping of circulating CD8+ T cell subsets in human cutaneous leishmaniasis

Cited by 22 publications

References 45 publications

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

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

Protective and Pathological Functions of CD8⁺T Cells in Leishmania braziliensis Infection

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Phenotyping of circulating CD8+ T cell subsets in human cutaneous leishmaniasis

Cited by 22 publications

References 45 publications

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

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

Protective and Pathological Functions of CD8+T Cells in Leishmania braziliensis Infection

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

Protective and Pathological Functions of CD8⁺T Cells in Leishmania braziliensis Infection