Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea

Hernández-Ruiz, Joselín; Becker, Ingeborg

doi:10.1590/s0036-36342006000500009

Cited by 8 publications

(7 citation statements)

References 81 publications

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“…Interestingly, there was no difference in the percentage of Annexin-5 + cells (Fig. S3), suggesting that cells from arg − L. major -infected mice were not undergoing more apoptosis than those from WT L. major -infected mice as previously suggested in diffused cutaneous leishmaniasis (50). …”

Section: Resultssupporting

confidence: 60%

“…Interaction of PD-1 with its ligand PD-L1 or PD-L2, negatively regulates cytokine production and T cell proliferation. Recently, PD-1-mediated exhaustion of CD8 + T cells has been linked to increased susceptibility to L. donovani (37) and L. mexicana infections in humans (50) and mice (36). Although T-cell exhaustion in leishmaniasis has been described for CD8 + T cells, CD4 + T cell exhaustion has not been demonstrated in this disease.…”

Section: Discussionmentioning

confidence: 99%

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Parasite-Derived Arginase Influences Secondary Anti-LeishmaniaImmunity by Regulating Programmed Cell Death-1–Mediated CD4+ T Cell Exhaustion

Mou

Muleme

Liu

et al. 2013

The Journal of Immunology

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The breakdown of L-arginine to ornithine and urea by host arginase supports Leishmania proliferation in macrophages. Studies using arginase-null mutants show that Leishmania-derived arginase plays an important role in disease pathogenesis. We investigated the role of parasite-derived arginase in secondary (memory) anti-Leishmania immunity in the resistant C57BL/6 mice. We found that C57BL/6 mice infected with arginase deficient (arg−) L. major failed to completely resolve their lesion and maintained chronic pathology after 16 weeks, a time when the lesion induced by wild type (WT) L. major is completely resolved. This chronic disease was associated with impaired antigen-specific proliferation and IFN-γ production, a concomitant increase in programmed cell death-1 (PD-1) expression on CD4+ T cells and failure to induce protection against secondary L. major challenge. Treatment with anti-PD-1 monoclonal antibody restored T cell proliferation and IFN-γ production in vitro and led to complete resolution of chronic lesion in arg− L. major-infected mice. These results show that infection with arg− L. major results in chronic disease due in part to PD-1-mediated clonal exhaustion of T cells, suggesting that parasite-derived arginase contributes to the overall quality of the host immune response and subsequent disease outcome in L. major-infected mice. They also indicate that persistent parasites alone do not regulate the quality of secondary anti-Leishmania immunity in mice and that the quality of the primary immune response may be playing a hitherto unrecognized dominant role in this process.

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Section: Resultssupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Parasite-Derived Arginase Influences Secondary Anti-LeishmaniaImmunity by Regulating Programmed Cell Death-1–Mediated CD4+ T Cell Exhaustion

Mou

Muleme

Liu

et al. 2013

The Journal of Immunology

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“…These data indicate that CD8 ϩ T cells are able to induce apoptosis in both groups but suggest that CD8 ϩ T cells from SC individuals are less cytotoxic than CD8 ϩ T cells from CL patients. To determine the specific cytotoxic effects exerted by CD8 ϩ T cells, the cytotoxicity index (CI) was calculated as previously described (25,26). CL patients had a CI of 8.3 Ϯ 5.3, which was higher than those for SC individuals (4.8 Ϯ 3.6) and the HC group (4.5 Ϯ 3.6) (P Ͻ 0.05) (Fig.…”

Section: Cd8mentioning

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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“…Lutzomyia is the main vector of Leishmania in North America, whereas Phlebotomus is the main vector in Europe, Asia, and Africa (Rodríguez Domínguez 2002, Salotra and Singh 2005, Reithinger et al 2007. Clinical forms of leishmaniasis include cutaneous (CL, localized or diffuse), which is characterized by ulcerative lesions on the skin, mucocutaneous (MCL), which exhibits destruction of the mucosal tissue, and visceral (VL or Kala-Azar), which affects various organs and is potentially lethal (Rodríguez Domínguez 2002, Salotra and Singh 2005, Hernández-Ruiz and Becker 2006, Reithinger et al 2007). In Mexico Leishmania donovani, Leishmania mexicana, and Leishmania braziliensis have been reported as causative agents of human leishmaniasis (Sanchez-Tejeda et al 2001, Pérez-Vega et al 2009, with the last two species responsible for CL and MCL lesions, respectively.…”

Section: Introductionmentioning

confidence: 99%

Molecular Diagnosis of Leishmania mexicana in a Cutaneous Leishmaniasis Case in Sinaloa, Mexico

Ochoa-Diaz

López-Moreno

Rendón-Maldonado

et al. 2012

Vector-Borne and Zoonotic Diseases

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Leishmaniasis has been considered endemic in Sinaloa, Mexico, since 1994. Despite that Leishmania mexicana is the main etiological agent of cutaneous leishmaniasis (CL) in other regions of Mexico, the species causing CL in patients from Sinaloa state has not been previously established, although Leishmania braziliensis has been found in the neighboring southern state, Nayarit. L. braziliensis is also associated with mucocutaneous leishmaniasis, which is a more complicated clinical variant. Due to the implications on individual and public health, the objective of this report was to identify the Leishmania species present in Sinaloa, Mexico. Using the first internal transcribed spacer (ITS-1) polymerase chain reaction-restriction fragment length polymorphism, we identified L. mexicana in a CL patient from Sinaloa and confirmed the extended distribution of this parasite in Mexico.

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Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea

Cited by 8 publications

References 81 publications

Parasite-Derived Arginase Influences Secondary Anti-LeishmaniaImmunity by Regulating Programmed Cell Death-1–Mediated CD4+ T Cell Exhaustion

Parasite-Derived Arginase Influences Secondary Anti-LeishmaniaImmunity by Regulating Programmed Cell Death-1–Mediated CD4+ T Cell Exhaustion

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

Molecular Diagnosis of Leishmania mexicana in a Cutaneous Leishmaniasis Case in Sinaloa, Mexico

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Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea

Cited by 8 publications

References 81 publications

Parasite-Derived Arginase Influences Secondary Anti-LeishmaniaImmunity by Regulating Programmed Cell Death-1–Mediated CD4+ T Cell Exhaustion

Parasite-Derived Arginase Influences Secondary Anti-LeishmaniaImmunity by Regulating Programmed Cell Death-1–Mediated CD4+ T Cell Exhaustion

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

Molecular Diagnosis of Leishmania mexicana in a Cutaneous Leishmaniasis Case in Sinaloa, Mexico

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