CCR7+ Central and CCR7− Effector Memory CD4+ T Cells in Human Cutaneous Leishmaniasis

Valian, Hossein Keshavarz; Rostami, Mahmoud Nateghi; Tasbihi, Minoo; Mohammadi, Akram Miramin; Eskandari, Seyed Ebrahim; Sarrafnejad, Abdolfattah

doi:10.1007/s10875-012-9788-7

Cited by 29 publications

(23 citation statements)

References 49 publications

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“…Giving support to our data, previous observation in mouse model of L. major infection indicates that effector memory CD4+ T cells are the main source of IFN-gamma [8]. Also, it was shown that in subjects with history of CL caused by L. major or L. tropica , effector memory CD4+ T cells were the main source of IFN-gamma production [26]. …”

Section: Discussionsupporting

confidence: 88%

Immunologic response and memory T cells in subjects cured of tegumentary leishmaniasis

et al. 2013

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BackgroundThe main clinical forms of tegumentary leishmaniasis are cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). L.braziliensis infection is characterized by an exaggerated production of IFN-gamma and TNF-alpha, cytokines involved in parasite destruction, but also in the pathology. Maintenance of an antigen-specific immune response may be important for resistance to re-infection and will contribute for vaccine development. In the present work we investigated the immune response in CL and ML cured individuals.MethodsParticipants in the present study included 20 CL and 20 ML patients, who were evaluated prior to, as well as 2 to 15 years after therapy. IFN-gamma, IL-2 and TNF-alpha production were determined by ELISA in supernatants of mononuclear cells stimulated with soluble L.braziliensis antigen (SLA). The frequency of memory CD4+ T cell populations was determined by FACS.ResultsHere we show that the majority of CL and ML patients did not produce in vitro IFN-gamma in response to SLA after cure. In the cured individuals who responded to SLA, effector memory (CD45RA-CCR7-) CD4+ T cells were the ones producing IFN-gamma. Because a large percent of CL and ML cured patients lost SLA-induced IFN-gamma production in peripheral blood, we performed Leishmania skin test (LST). A positive LST was found in 87.5% and 100% of CL and ML cured individuals, respectively, who did not produce IFN-gamma or IL-2 in vitro.ConclusionThis study shows that in spite of losing in vitro antigen-specific response to Leishmania, cured CL and ML subjects retain the ability to respond to SLA in vivo. These findings indicate that LST, rather than IFN-gamma production, may be a better assessment of lasting immunity to leishmaniasis in human studies, and thus a better tool for assessing immunization after vaccine. Furthermore, in cured individuals which maintains Leishmania-specific IFN-gamma production, effector memory CD4+ T cells were the main source of this cytokine.

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Section: Discussionsupporting

confidence: 88%

Immunologic response and memory T cells in subjects cured of tegumentary leishmaniasis

et al. 2013

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“…This is important as it allows comparison of the cytokines alterations in a given patient from active‐phase to healed lesions. However, in most of the published data on human leishmaniasis, immune responses of subjects with active and with history of CL have been measured separately, and due to the broad variations of immune responses in every individual, the interpretation of these data may not be always concomitant with precision . The results of the present study showed that TNF‐α levels are significantly reduced in all patients with CL after standard treatment with antimony and clinical cure of lesions, although the intensity of the reductions was different among CL volunteers.…”

Section: Discussionmentioning

confidence: 56%

“…In human leishmaniasis, the mechanisms of protection have not been fully understood, although the phenotypes and effector functions of CD8 + T cells and CD4 + Th1/Th2 lymphocytes have been extensively studied , and the presence of Th17 cells in the skin lesion samples of patients with active CL and role of Th17 cytokines in support of Th1 response in patients with VL have been demonstrated . The role of a number of immune system productions, such as pro‐inflammatory cytokine TNF‐α, IL‐17 and IL‐22 in CL outcome, needs more clarification.…”

Section: Introductionmentioning

confidence: 99%

Tumour Necrosis Factor‐alpha (TNF‐α) and its soluble receptor type 1 (sTNFR I) in human active and healed leishmaniases

Rostami

Jasbi

Khamesipour

2016

Parasite Immunology

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The role of tumour necrosis factor-alpha (TNF-α) is not fully understood in human leishmaniasis. We analysed the alterations in the levels of TNF-α, soluble TNF receptor type 1 (sTNFR I), IL-17 and IL-22 productions in active and healed leishmaniases. Blood samples were collected from volunteers with active cutaneous leishmaniasis (ACL), the same subjects after lesion healing (healed CL = HCL), volunteers with active visceral leishmaniasis (AVL), healed VL (HVL) and healthy controls. Levels of cytokines were titrated on Leishmania Ag-stimulated PBMC culture. The mean level of TNF-α production from stimulated cells was significantly higher in ACL than controls (P < 0·001) and significantly reduced after treatment in HCL volunteers (P < 0·05). The mean level of sTNFR I production was significantly higher in ACL than controls (P < 0·001) and significantly reduced after treatment in HCL volunteers (P < 0·05). The mean level of IL-22 production in AVL was significantly higher than controls (P < 0·05) and was significantly lower in HVL compared with AVL (P < 0·001) and controls (P < 0·05). The levels of TNF-α (P = 0·0025) and sTNFR I (P < 0·01) productions from PBMCs showed significant decreasing trend after treatment in each CL volunteer. Reduction in TNF-α is associated with clinical response to treatment and healing of CL lesions due to L. major.

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“…CCR7 + CD4 memory cells that show increased proliferative capacity in response to leishmania antigen have been identified in cutaneous leishmaniasis patients that have healed [66], suggesting that T CM cells are generated by infection in humans and may be a good target in a vaccine.…”

Section: Implications For the Development Of A Cutaneous Leishmanimentioning

confidence: 99%

Memory T cells in cutaneous leishmaniasis

Glennie

Scott

2016

Cellular Immunology

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Leishmania causes a spectrum of diseases that range from self-healing to fatal infections. Control of leishmania is dependent upon generating CD4+ Th1 cells that produce IFNγ, leading to macrophage activation and killing of the intracellular parasites. Following resolution of the disease, short-lived effector T cells, as well as long-lived central memory T cells and skin resident memory T cells, are retained and able to mediate immunity to a secondary infection. However, there is no vaccine for leishmaniasis, and the drugs used to treat the disease can be toxic and ineffective. While a live infection generates immunity, a successful vaccine will depend upon generating memory T cells that can be maintained without the continued presence of parasites. Since both central memory and skin resident memory T cells are long-lived, they may be the appropriate targets for a leishmaniasis vaccine.

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CCR7+ Central and CCR7− Effector Memory CD4+ T Cells in Human Cutaneous Leishmaniasis

Cited by 29 publications

References 49 publications

Immunologic response and memory T cells in subjects cured of tegumentary leishmaniasis

Immunologic response and memory T cells in subjects cured of tegumentary leishmaniasis

Tumour Necrosis Factor‐alpha (TNF‐α) and its soluble receptor type 1 (sTNFR I) in human active and healed leishmaniases

Memory T cells in cutaneous leishmaniasis

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