CD8 cytotoxic T cells in cutaneous leishmaniasis

Ruiz, Juan Luis Jiménez; Becker, I.

doi:10.1111/j.1365-3024.2007.00991.x

Cited by 71 publications

(68 citation statements)

References 68 publications

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“…ϩ T cells incubated with Leishmania-infected monocytes minus number of CD14 ϩ annexin V ϩ cells among CD8 ϩ T cells incubated with uninfected monocytes (24).…”

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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“…ϩ T cells incubated with Leishmania-infected monocytes minus number of CD14 ϩ annexin V ϩ cells among CD8 ϩ T cells incubated with uninfected monocytes (24).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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“…52 However, the present perception of CD8 + T cells has changed with significant observations of failure of CD8 + T cell-deficient mice to control parasitic growth suggesting that CD8 + T cells play an important role in immunity against infection with L. major. [53][54][55] There are also data that strongly support the crucial role of CD8 + T cells not only in primary response to infection in experimental VL but also as major mediators of resistance upon reinfection. [56][57][58][59] In order to analyze the relative contribution of CD4 + and CD8 + IFNγ-producing T cells in protection elicited in our experimental model, the percentage of these populations in spleen cells of vaccinated and infected mice was determined.…”

mentioning

confidence: 98%

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Margaroni¹,

Agallou²,

Athanasiou³

et al. 2017

IJN

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Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble Leishmania infantum antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with L. infantum parasites in BALB/c mice. Vaccination with these multifunctionalized PLGA nanoformulations conferred significant protection against parasite infection in vaccinated mice. In particular, vaccination with PLGA-sLiAg-MPLA or p8-PLGA-sLiAg NPs resulted in almost complete elimination of the parasite in the spleen for up to 4 months post-challenge. Parasite burden reduction was accompanied by antigen-specific humoral and cellular immune responses. Specifically, injection with PLGA-sLiAg-MPLA raised exclusively anti-sLiAg IgG1 antibodies post-vaccination, while in p8-PLGA-sLiAg-vaccinated mice, no antibody production was detected. However, 4 months post-challenge, in mice vaccinated with all the multifunctionalized NPs, antibody class switching towards IgG2a subtype was observed. The study of cellular immune responses revealed the increased proliferation capacity of spleen cells against sLiAg, consisting of IFNγ-producing CD4 + and CD8 + T cells. Importantly, the activation of CD8 + T cells was exclusively attributed to vaccination with PLGA NPs surface-modified with the p8 peptide. Moreover, characterization of cytokine production in vaccinated–infected mice revealed that protection was accompanied by significant increase of IFNγ and lower levels of IL-4 and IL-10 in protected mice when compared to control infected group. Conclusively, the above nanoformulations hold promise for future vaccination strategies against VL.

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“…It is found that there is an alteration in the cellular response T-helper (Th)-2 type, which is associated with a specific cell anergy to leishmania antigens and manifested by a negative Montenegro reaction. 8 Also, there is a low level of CD-8 T lymphocytes, which plays an important role against infection by being a potential target for a vaccine development. 9 Important for development of immunotherapy agents, they can exert their effect by directly or indirectly augmenting the host natural defenses, thereby restoring the impaired effector functions or decreasing host excessive and deleterious response to the parasite.…”

Section: Discussionmentioning

confidence: 99%

Transient Success Using Prolonged Treatment with Miltefosine for a Patient with Diffuse Cutaneous Leishmaniasis Infected with Leishmania mexicana mexicana

Ordáz-Farías

Muñoz-Garza

Sevilla-Gonzalez

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Leishmania sp. is an intracellular parasite that causes a variable degree of clinical manifestations, especially in the skin. We present the case of a 38-year-old male with a chronic history of mucocutaneous disease present since childhood that generated deformity, loss of cartilage in the ears and nose, and scarring that limited his range of motion. The parasite was identified as L. mexicana mexicana. The patient was treated with a 3-month course of oral miltefosine with overwhelming results.

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CD8 cytotoxic T cells in cutaneous leishmaniasis

Cited by 71 publications

References 68 publications

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

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

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Transient Success Using Prolonged Treatment with Miltefosine for a Patient with Diffuse Cutaneous Leishmaniasis Infected with Leishmania mexicana mexicana

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CD8 cytotoxic T cells in cutaneous leishmaniasis

Cited by 71 publications

References 68 publications

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

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

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNF&alpha;-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Transient Success Using Prolonged Treatment with Miltefosine for a Patient with Diffuse Cutaneous Leishmaniasis Infected with Leishmania mexicana mexicana

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Product

Resources

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

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

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis