Multifunctional CD4+T cells in patients with American cutaneous leishmaniasis

Macedo, Amanda B.; Sánchez‐Arcila, Juan Camilo; Schubach, Armando; Mendonça, Sergio C. F.; Marins-Dos-Santos, Alessandro; Madeira, Maria de Fátima; Gagini, Thalita; Pimentel, Maria Inês Fernandes; Luca, Paula Mello De

doi:10.1111/j.1365-2249.2011.04536.x

Cited by 33 publications

(42 citation statements)

References 62 publications

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“…These authors also showed increased MFI for IFNγ and TNFα. Recently, it has been also reported the presence of this high quality, multifunctional CD4 + T cells in peripheral blood mononuclear cells of patients that healed American cutaneus leishmaniasis, and the same phenomenon was observed in the MFI for IFNγ, IL-2 and TNFα, thus supporting the significance of our findings [41]. In fact, in our DNA-LACK/MVA-LACK system we also observed multifunctional CD4+ T cells that secrete IFNγ, IL-2 and TNFα, but in addition we obtained CD8 + T cell responses which are also polyfunctional.…”

Section: Discussionsupporting

confidence: 90%

High Quality Long-Term CD4+ and CD8+ Effector Memory Populations Stimulated by DNA-LACK/MVA-LACK Regimen in Leishmania major BALB/c Model of Infection

et al. 2012

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Heterologous vaccination based on priming with a plasmid DNA vector and boosting with an attenuated vaccinia virus MVA recombinant, with both vectors expressing the Leishmania infantum LACK antigen (DNA-LACK and MVA-LACK), has shown efficacy conferring protection in murine and canine models against cutaneus and visceral leishmaniasis, but the immune parameters of protection remain ill defined. Here we performed by flow cytometry an in depth analysis of the T cell populations induced in BALB/c mice during the vaccination protocol DNA-LACK/MVA-LACK, as well as after challenge with L. major parasites. In the adaptive response, there is a polyfunctional CD4+ and CD8+ T cell activation against LACK antigen. At the memory phase the heterologous vaccination induces high quality LACK-specific long-term CD4+ and CD8+ effector memory cells. After parasite challenge, there is a moderate boosting of LACK-specific CD4+ and CD8+ T cells. Anti-vector responses were largely CD8+-mediated. The immune parameters induced against LACK and triggered by the combined vaccination DNA/MVA protocol, like polyfunctionality of CD4+ and CD8+ T cells with an effector phenotype, could be relevant in protection against leishmaniasis.

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Section: Discussionsupporting

confidence: 90%

High Quality Long-Term CD4+ and CD8+ Effector Memory Populations Stimulated by DNA-LACK/MVA-LACK Regimen in Leishmania major BALB/c Model of Infection

et al. 2012

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“…Darrah et al demonstrated for L. major that expansion of multifunctional CD4 ϩ T cells secreting IFN-␥, IL-2, and TNF-␣ strongly correlates with protection against subsequent challenge (76). Furthermore, the presence of high-quality, multifunctional CD4 ϩ T cells in peripheral blood mononuclear cells of patients that healed American cutaneous leishmaniasis, thus supporting the significance of our findings, has also been reported (77). The increase in the frequency of CD4 ϩ T cells observed in the animals inoculated with M65-LACK virus that can be explained by a higher persistence of heterologous antigen due to an increased replication capacity is remarkable (78).…”

Section: Discussionsupporting

confidence: 77%

Attenuated and Replication-Competent Vaccinia Virus Strains M65 and M101 with Distinct Biology and Immunogenicity as Potential Vaccine Candidates against Pathogens

Sánchez-Sampedro

Gómez

Mejías-Pérez

et al. 2013

J Virol

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“…These changes correlate with the impaired T cells responses observed by other groups [17, 54], implying a poor quality of T cell responses to L. amazonensis antigens. This notion is further supported by a recent study of Macedo et al [55], which compared the quality of T cell responses induced by promastigote crude antigens of L. braziliensis and L. amazonensis in PBMCs from healed CL patients. Their multi-parametric flow cytometric studies indicated that L. braziliensis antigens induced an important proportion of multi-cytokine-producing CD4 + T cells (28 % of the total Th1 response evaluated), whereas L. amazonensis antigens mostly (68 %) induced single-positive cells, 57 % of which were IFN-γ single positives.…”

Section: Non-healing Human Diseases Associated With L Amazonensis Anmentioning

confidence: 62%

Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis

2012

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The outcomes of Leishmania infection are determined by host immune and nutrition status, parasite species, and co-infection with other pathogens. While subclinical infection and self-healing cutaneous leishmaniasis (CL) are common, uncontrolled parasite replication can lead to non-healing local lesions or visceral leishmaniasis (VL). It is known that infection control requires Th1-differentiation cytokines (IL-12, IL-18, and IL-27) and Th1 cell and macrophage activation. However, there is no generalized consensus for the mechanisms of host susceptibility. The recent studies on regulatory T cells and IL-17-producing cells help explain the effector T cell responses that occur independently of the known Th1/Th2 cell signaling pathways. This review focuses on the immunopathogenesis of non-healing American CL and progressive VL. We summarize recent evidence from human and animal studies that reveals the mechanisms of dysregulated, hyper-responses to Leishmania braziliensis, as well as the presence of disease-promoting or the absence of protective responses to Leishmania amazonensis and Leishmania donovani. We highlight immune-mediated parasite growth and immunopathogenesis, with an emphasis on the putative roles of IL-17 and its related cytokines as well as arginase. A better understanding of the quality and regulation of innate immunity and T cell responses triggered by Leishmania will aid in the rational control of pathology and the infection.

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Multifunctional CD4+T cells in patients with American cutaneous leishmaniasis

Cited by 33 publications

References 62 publications

High Quality Long-Term CD4+ and CD8+ Effector Memory Populations Stimulated by DNA-LACK/MVA-LACK Regimen in Leishmania major BALB/c Model of Infection

High Quality Long-Term CD4+ and CD8+ Effector Memory Populations Stimulated by DNA-LACK/MVA-LACK Regimen in Leishmania major BALB/c Model of Infection

Attenuated and Replication-Competent Vaccinia Virus Strains M65 and M101 with Distinct Biology and Immunogenicity as Potential Vaccine Candidates against Pathogens

Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis

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