Adoptive Immunotherapy against Experimental Visceral Leishmaniasis with CD8<sup>+</sup>T Cells Requires the Presence of Cognate Antigen

Polley, Rosalind; Stäger, Simona; Prickett, Sara; Maroof, Asher; Zubairi, Soombul; Smith, Deborah F.; Kaye, Paul M.

doi:10.1128/iai.74.1.773-776.2006

Cited by 61 publications

(61 citation statements)

References 26 publications

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“…Taken together, these studies indicate that the ability to recruit naive T cells into an ongoing immune response will vary, presumably depending upon specific characteristics of the infection. Similarly, adoptive transfer of naive OT-I cells into mice infected for 3 wk with OVA-transgenic Leishmania donovani was host protective, albeit with delayed kinetics compared with transfer of previously activated OT-I cells (51).…”

Section: Discussionmentioning

confidence: 99%

Antigen-Experienced T Cells Limit the Priming of Naive T Cells during Infection withLeishmania major

Gray

Reiner

Smith

et al. 2006

The Journal of Immunology

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One mechanism to control immune responses following infection is to rapidly down-regulate Ag presentation, which has been observed in acute viral and bacterial infections. In this study, we describe experiments designed to address whether Ag presentation is decreased after an initial response to Leishmania major. Naive αβ-Leishmania-specific (ABLE) TCR transgenic T cells were adoptively transferred into mice at various times after L. major infection to determine the duration of presentation of parasite-derived Ags. ABLE T cells responded vigorously at the initiation of infection, but the ability to prime these cells quickly diminished, independent of IL-10, regulatory T cells, or Ag load. However, Ag-experienced clonal and polyclonal T cell populations could respond, indicating that the diminution in naive ABLE cell responses was not due to lack of Ag presentation. Because naive T cell priming could be restored by removal of the endogenous T cell population, or adoptive transfer of Ag-pulsed dendritic cells, it appears that T cells that have previously encountered Ag during infection compete with naive Ag-specific T cells. These results suggest that during L. major infection Ag-experienced T cells, rather than naive T cells, may be primarily responsible for sustaining the immune response.

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Section: Discussionmentioning

confidence: 99%

Antigen-Experienced T Cells Limit the Priming of Naive T Cells during Infection withLeishmania major

Gray

Reiner

Smith

et al. 2006

The Journal of Immunology

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“…The gating strategy used is shown (top panels). Parasites and infections L. donovani (LV9) and OVA-transgenic LV9 (PINK LV9) (22) were maintained by passage in B6.RAG1 2/2 mice, and amastigotes were isolated from the spleens of chronically infected mice. Mice were infected by injecting 2 3 10 7 amastigotes i.v.…”

Section: Figure 1 Ag-specific Cd4mentioning

confidence: 99%

“…To assess Ag-specific T cell proliferation in vivo, mice were infected with OVA-transgenic PINK LV9 (22). Splenic OVA-specific OT II T cells were isolated and labeled with CFSE, as previously described (26).…”

Section: Cd4 + T Cell Proliferationmentioning

confidence: 99%

Tissue Requirements for Establishing Long-Term CD4+ T Cell–Mediated Immunity following Leishmania donovani Infection

Bunn

Stanley

Rivera

et al. 2014

The Journal of Immunology

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Organ-specific immunity is a feature of many infectious diseases, including visceral leishmaniasis caused by Leishmania donovani. Experimental visceral leishmaniasis in genetically susceptible mice is characterized by an acute, resolving infection in the liver and chronic infection in the spleen. CD4+ T cell responses are critical for the establishment and maintenance of hepatic immunity in this disease model, but their role in chronically infected spleens remains unclear. In this study, we show that dendritic cells are critical for CD4+ T cell activation and expansion in all tissue sites examined. We found that FTY720-mediated blockade of T cell trafficking early in infection prevented Ag-specific CD4+ T cells from appearing in lymph nodes, but not the spleen and liver, suggesting that early CD4+ T cell priming does not occur in liver-draining lymph nodes. Extended treatment with FTY720 over the first month of infection increased parasite burdens, although this associated with blockade of lymphocyte egress from secondary lymphoid tissue, as well as with more generalized splenic lymphopenia. Importantly, we demonstrate that CD4+ T cells are required for the establishment and maintenance of antiparasitic immunity in the liver, as well as for immune surveillance and suppression of parasite outgrowth in chronically infected spleens. Finally, although early CD4+ T cell priming appeared to occur most effectively in the spleen, we unexpectedly revealed that protective CD4+ T cell–mediated hepatic immunity could be generated in the complete absence of all secondary lymphoid tissues.

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“…[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. Vaccination with p8-PLGA-sLiAg or p8-PLGAsLiAg-MPLA significantly enhanced CD3…”

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confidence: 99%

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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Adoptive Immunotherapy against Experimental Visceral Leishmaniasis with CD8⁺T Cells Requires the Presence of Cognate Antigen

Cited by 61 publications

References 26 publications

Antigen-Experienced T Cells Limit the Priming of Naive T Cells during Infection withLeishmania major

Antigen-Experienced T Cells Limit the Priming of Naive T Cells during Infection withLeishmania major

Tissue Requirements for Establishing Long-Term CD4+ T Cell–Mediated Immunity following Leishmania donovani 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

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Adoptive Immunotherapy against Experimental Visceral Leishmaniasis with CD8+T Cells Requires the Presence of Cognate Antigen

Cited by 61 publications

References 26 publications

Antigen-Experienced T Cells Limit the Priming of Naive T Cells during Infection withLeishmania major

Antigen-Experienced T Cells Limit the Priming of Naive T Cells during Infection withLeishmania major

Tissue Requirements for Establishing Long-Term CD4+ T Cell–Mediated Immunity following Leishmania donovani 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

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Resources

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Adoptive Immunotherapy against Experimental Visceral Leishmaniasis with CD8⁺T Cells Requires the Presence of Cognate Antigen

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