Differential T Cell Responses to Residual Viral Antigen Prolong CD4+ T Cell Contraction following the Resolution of Infection

Misumi, Ichiro; Alirezaei, Mehrdad; Eam, Boreth; Su, Maureen A.; Whitton, J. Lindsay; Whitmire, Jason K.

doi:10.4049/jimmunol.1301215

Cited by 7 publications

(5 citation statements)

References 76 publications

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“…The present results suggest that antigenic signals were not involved in regulating contraction, consistent with findings that the dose and duration of infection do not influence contraction (4,6). Moreover CD8 + T cells do not undergo cell division in response to residual Ag (50), and C3 deficiency does not affect the ability of DCs to present Ag in vitro or during the maturation of DCs in vivo after L. monocytogenes infection (35). In contrast, we found that the levels of critical cytokines, such as IL-12 and IFN-g, were reduced 24 h postinfection.…”

Section: Discussionsupporting

confidence: 78%

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Tan

et al. 2014

The Journal of Immunology

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Ag-specific CD8+ T cell contraction (contraction), which occurs after the resolution of infection, is critical for homeostasis of the immune system. Although complement components regulate the primary CD8+ T cell response, there is insufficient evidence supporting their role in regulating contraction and memory. In this study, we show that C3-deficient (C3−/−) mice exhibited significantly less CD8+ T cell contraction than did wild-type mice postinfection with recombinant Listeria monocytogenes expressing OVA. Kinetic analyses also revealed decreased contraction in mice treated with cobra venom factor to deplete C3, which was consistent with the results in C3−/− recipient mice transplanted with bone marrow cells from the same donors as wild-type recipient mice. The phenotypes of memory cells generated by C3−/− mice were not altered compared with those of wild-type mice. Further, C5aR signaling downstream of C3 was not involved in the regulation of contraction. Moreover, the regulation of contraction by C3 may be independent of the duration of antigenic stimulation or the functional avidity of effector CD8+ T cells. However, reduced contraction in C3−/− mice was accompanied by a decrease in the proportion of KLRG-1hi (killer-cell lectin-like receptor G1) CD127lo short-lived effector cells at the peak of the response and correlated with a reduction in the levels of inflammatory cytokines, such as IL-12 and IFN-γ, produced early postinfection. These results provide new insights into the role of systemic C3 in regulating contraction following intracellular bacterial infection and may help to develop vaccines that are more effective.

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Section: Discussionsupporting

confidence: 78%

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Tan

et al. 2014

The Journal of Immunology

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“…Slow contraction of CD4+ T cells paralleled gradual clearance of HAV RNA from the liver over 8–9 months [12,32]. While the continued presence of intrahepatic HAV RNA for such a long period of time was unexpected, it is consistent with a role for residual viral antigen in prolonging CD4+ but not CD8+ T cell contraction as described recently in lymphocytic choriomeningitis virus (LCMV)-infected mice [33]. …”

Section: Adaptive Immunity and Control Of Hav Infectionsupporting

confidence: 57%

Reassessing immune control of hepatitis A virus

Walker

Feng

Lemon

2015

Current Opinion in Virology

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There is renewed interest in hepatitis A virus (HAV) pathogenesis and immunity after 2–3 decades of limited progress. From a public health perspective, the average age at infection has increased in developing countries, resulting in more severe hepatitis that is poorly understood mechanistically. More fundamentally, there is interest in comparing immunity to HAV and hepatitis C virus (HCV): small, positive-strand RNA viruses with very different infection outcomes. Here, we review evidence that circulating HAV virions are cloaked in membranes, with consequences for induction of innate immunity and antibody-mediated neutralization. We also consider the contribution of CD4+ helper versus CD8+ cytotoxic T cells to antiviral immunity and liver injury, and present a model of non-cytotoxic immune control of HAV infection.

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“…It is thus tempting to speculate that the capability of CD8 + T cells to respond to a short Ag pulse might reflect transient viral gene transcription and its preferred feeding of the class I pathway. The fact that CD4 + T cells respond much longer to residual Ag following viral clearance than CD8 + T cells do also indicates that antiviral CD8 + T cell responses depend on viral transcription (79,80).…”

Section: Discussionmentioning

confidence: 99%

Differential Kinetics of Antigen Dependency of CD4+ and CD8+ T Cells

Rabenstein

Ellwart

et al. 2014

The Journal of Immunology

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Ag recognition via the TCR is necessary for the expansion of specific T cells that then contribute to adaptive immunity as effector and memory cells. Because CD4+ and CD8+ T cells differ in terms of their priming APCs and MHC ligands we compared their requirements of Ag persistence during their expansion phase side by side. Proliferation and effector differentiation of TCR transgenic and polyclonal mouse T cells were thus analyzed after transient and continuous TCR signals. Following equally strong stimulation, CD4+ T cell proliferation depended on prolonged Ag presence, whereas CD8+ T cells were able to divide and differentiate into effector cells despite discontinued Ag presentation. CD4+ T cell proliferation was neither affected by Th lineage or memory differentiation nor blocked by coinhibitory signals or missing inflammatory stimuli. Continued CD8+ T cell proliferation was truly independent of self-peptide/MHC-derived signals. The subset divergence was also illustrated by surprisingly broad transcriptional differences supporting a stronger propensity of CD8+ T cells to programmed expansion. These T cell data indicate an intrinsic difference between CD4+ and CD8+ T cells regarding the processing of TCR signals for proliferation. We also found that the presentation of a MHC class II–restricted peptide is more efficiently prolonged by dendritic cell activation in vivo than a class I bound one. In summary, our data demonstrate that CD4+ T cells require continuous stimulation for clonal expansion, whereas CD8+ T cells can divide following a much shorter TCR signal.

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Differential T Cell Responses to Residual Viral Antigen Prolong CD4+ T Cell Contraction following the Resolution of Infection

Cited by 7 publications

References 76 publications

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Reassessing immune control of hepatitis A virus

Differential Kinetics of Antigen Dependency of CD4+ and CD8+ T Cells

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