Kinetic and Mechanistic Requirements for Helping CD8 T Cells

Agnellini, Paola; Wiesel, Melanie; Schwarz, Katrin; Wolint, Petra; Bachmann, Martin F.; Oxenius, Annette

doi:10.4049/jimmunol.180.3.1517

Cited by 24 publications

(42 citation statements)

References 52 publications

(104 reference statements)

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“…This impaired memory is unfortunate, but it probably is inherent to the CD4 T cell-deficient environment, because even CD8 + T cells primed in the presence of CD4 + T cell help are less stable following transfer into MHC class II-deficient mice compared with WT recipients (35). Fortunately, as is also evident from these and other experiments, the CD4 + T cells do not need to be Ag specific; thus, only the application of vaccines in the most severely CD4 + T cell-deficient hosts would suffer markedly from this complication (35,36).…”

Section: Discussionmentioning

confidence: 66%

Vaccination against Lymphocytic Choriomeningitis Virus Infection in MHC Class II-Deficient Mice

Holst

Christensen

Thomsen

2011

The Journal of Immunology

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The impact of prophylactic vaccination against acute and chronic infection in a Th-deficient host has not been adequately addressed because of difficulties in generating protective immunity in the absence of CD4+ T cell help. In this study, we demonstrated that a broad CD8+ T cell immune response could be elicited in MHC class II-deficient mice by vaccination with adenovirus encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein tethered to MHC class II-associated invariant chain. Moreover, the response induced conferred significant cytolytic CD8+ T cell-mediated protection against challenge with a high dose of the invasive clone 13 strain of LCMV. In contrast, vaccination with adenovirus encoding unlinked LCMV glycoprotein induced weak virus control in the absence of CD4+ T cells, and mice may die of increased immunopathology associated with incomplete protection. Acute mortality was not observed in any vaccinated mice following infection with the less-invasive Traub strain. However, LCMV Traub infection caused accelerated late mortality in unvaccinated MHC class II-deficient mice; in this case, we observed a strong trend toward delayed mortality in vaccinated mice, irrespective of the nature of the vaccine. These results indicated that optimized vaccination may lead to efficient protection against acute viral infection, even in Th-deficient individuals, but that the duration of such immunity is limited. Nevertheless, for select immunodeficiencies in which CD4+ T cell deficiency is incomplete or transient, these results are very encouraging.

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Section: Discussionmentioning

confidence: 66%

Vaccination against Lymphocytic Choriomeningitis Virus Infection in MHC Class II-Deficient Mice

Holst

Christensen

Thomsen

2011

The Journal of Immunology

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“…Vaccination with NP-CpG-B and NP-OVA increased the proportion of CD8 + T cells capable of degranulating and secreting IFN-γ compared with vaccination with soluble CpG-B and NP-OVA. Frequencies of CD4 + T cells secreting both IFN-γ and TNF-α were also increased, which could have enhanced the cytotoxic potential of the CD8 + T cells (29). Interestingly, at the adjuvant dose used, NP-CpG-B with NP-OVA was the only formulation inducing both CD8 + and CD4 + T-cell responses.…”

Section: Discussionmentioning

confidence: 90%

“…Asterisks indicate statistics between CpG-B and NP-CpG-B; pound signs indicate statistics between CpG-C and NP-CpG-C. CD4 + T cells capable of secreting both IFN-γ + and TNF-α + (Fig. 2B), reflecting potent CTL help (29). In accordance with this, only NP-CpG-B could significantly induce cytotoxic (IFN-γ + ) and degranulating (CD107a + ) CD8 + T-cell responses ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

Titta

Ballester

Julier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

236

218

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Significance High adjuvant doses are generally required to induce strong CD8 + T-cell immunity with subunit vaccines. Here we codeliver an antigen and an adjuvant coupled on separate ultrasmall polymeric nanoparticles. Because both payloads are attached to similarly sized nanoparticles, and as size is the principle determinant of nanoparticle drainage, this enhanced the dual uptake of antigen and adjuvant by cross-presenting dendritic cells resident in the draining lymph nodes. This cotargeting induced potent effector CD8 + T cells and a more powerful memory recall of these cytotoxic T cells compared with nanoparticle-conjugated antigen with free adjuvant. As such, nanoparticle conjugation enhanced the immunogenicity of adjuvants while maintaining a low dose, and thus limiting toxicity, affecting the design of future subunit vaccine formulations.

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“…For stainings, whole blood or single-cell suspensions from spleens were used; surface and intracellular cytokine stainings were performed as described previously (25). Annexin V stainings were performed according to the instructions of the manufacturer (BD Bioscience).…”

Section: Immunofluorescence Staining and Analysismentioning

confidence: 99%

Type I IFN Substitutes for T Cell Help during Viral Infections

Wiesel

Kratky

Oxenius

2011

The Journal of Immunology

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Certain virus infections depend on the presence of T cell help for the generation of primary CD8+ T cell responses. However, the mechanisms that render these particular viral infections T cell help dependent is largely unknown. In this study, we compared CD8+ T cell responses elicited by lymphocytic choriomeningitis virus infection, as prototype of a T cell help independent infection, with T cell help dependent CD8+ T cell responses induced by vaccinia virus infection. In this paper, we show that a key parameter decisive for T cell help independence is the ability of an infectious agent to stimulate early and robust production of type I IFN. Experimental provision of type I IFN during VV infection rendered the ensuing CD8+ T cell response completely T cell help independent. Our results support a model in which type I IFN has to be present during the first 3 d of Ag encounter and has to act directly on the responding CD8+ T cells to promote their survival and effector differentiation. We show that type I IFN signaling on responding CD8+ T cells induces profound upregulation of CD25 and increased IL-2 expression; however, neither this nor IL-15 accounts for the type I IFN effects on responding CD8+ T cells. Thus, type I IFN can effectively replace the requirement of T cell help by directly promoting CD8+ T cell survival and differentiation independent of the type I IFN-induced cytokines IL-2 and IL-15.

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Kinetic and Mechanistic Requirements for Helping CD8 T Cells

Cited by 24 publications

References 52 publications

Vaccination against Lymphocytic Choriomeningitis Virus Infection in MHC Class II-Deficient Mice

Vaccination against Lymphocytic Choriomeningitis Virus Infection in MHC Class II-Deficient Mice

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

Type I IFN Substitutes for T Cell Help during Viral Infections

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