Heterogeneity among Viral Antigen-Specific CD4+ T Cells and Their De Novo Recruitment during Persistent Polyomavirus Infection

Lin, Eaton; Kemball, Christopher C.; Hadley, Annette; Wilson, Joseph S.; Hofstetter, Amelia R.; Pack, Christopher D.; Lukacher, Aron E.

doi:10.4049/jimmunol.0904210

Cited by 19 publications

(17 citation statements)

References 56 publications

(60 reference statements)

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“…Thus, phagosomal pathogen p:MHCII-specific CD4 ϩ T cell populations are maintained by a nonclassical antigen-dependent mechanism. This mechanism has also been observed for polyomavirus p:MHCII-specific CD4 ϩ T cells in mice with persistent infection (131).…”

Section: Cd4 ؉ T Cell Response To Phagosomal Infectionsupporting

confidence: 55%

CD4⁺T Cells: Guardians of the Phagosome

Tubo

Jenkins

2014

Clin Microbiol Rev

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SUMMARY CD4 + T cells are key cells of the adaptive immune system that use T cell antigen receptors to recognize peptides that are generated in endosomes or phagosomes and displayed on the host cell surface bound to major histocompatibility complex molecules. These T cells participate in immune responses that protect hosts from microbes such as Mycobacterium tuberculosis , Cryptococcus neoformans , Leishmania major , and Salmonella enterica , which have evolved to live in the phagosomes of macrophages and dendritic cells. Here, we review studies indicating that CD4 + T cells control phagosomal infections asymptomatically in most individuals by secreting cytokines that activate the microbicidal activities of infected phagocytes but in a way that inhibits the pathogen but does not eliminate it. Indeed, we make the case that localized, controlled, persistent infection is necessary to maintain large numbers of CD4 + effector T cells in a state of activation needed to eradicate systemic and more pathogenic forms of the infection. Finally, we posit that current vaccines for phagosomal infections fail because they do not produce this “periodic reminder” form of CD4 + T cell-mediated immune control.

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Section: Cd4 ؉ T Cell Response To Phagosomal Infectionsupporting

confidence: 55%

CD4⁺T Cells: Guardians of the Phagosome

Tubo

Jenkins

2014

Clin Microbiol Rev

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“…CD4 T cells likely provide other forms of help aside from IL-2, as exogenous addition of IL-2 during the maintenance phase did not prevent decay of the Q9:VP2.139 population following CD4 + cell depletion. We have recently demonstrated that MPyV-specific CD4 T cells, in addition to producing IL-2, produce IFN-γ, TNF-α, IL-10 and IL-21 (44). IL-21 has been demonstrated to sustain CD8 T cells during chronic infection (45–47), and it is tempting to speculate that IL-21 signaling may also support the sustained expansion and maintenance of Q9:VP2.139-specific CD8 T cells.…”

Section: Discussionmentioning

confidence: 99%

MHC Class Ib-Restricted CD8 T Cells Differ in Dependence on CD4 T Cell Help and CD28 Costimulation over the Course of Mouse Polyomavirus Infection

Hofstetter

Ford

Sullivan

et al. 2012

The Journal of Immunology

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We recently identified a protective MHC class Ib-restricted CD8 T cell response to infection with mouse polyomavirus. These CD8 T cells recognize a peptide from aa 139–147 of the VP2 viral capsid protein bound to the nonpolymorphic H-2Q9 molecule, a member of the Qa-2 family of β2m-associated MHC-Ib molecules. Q9:VP2.139-specific CD8 T cells exhibit an unusual inflationary response characterized by a gradual expansion over 3 months followed by a stable maintenance phase. We previously demonstrated that Q9:VP2.139-specific CD8 T cells are dependent on Ag for expansion, but not for the long-term maintenance. Here, we tested the hypothesis that the expansion and maintenance components of the Q9:VP2.139-specific T cell response are differentially dependent on CD4 T cell help and CD28 costimulation. Depletion of CD4+ cells and CD28/CD40L blockade impaired expansion of Q9:VP2.139-specific CD8 T cells, and intrinsic CD28 signaling was sufficient for expansion. In contrast, CD4 T cell-insufficiency, but not CD28/CD40L blockade, resulted in a decline in frequency of Q9:VP2.139-specific CD8 T cells during the maintenance phase. These results indicate that the Q9:VP2.139-specific CD8 T cell response to mouse polyomavirus infection depends on CD4 T cell help and CD28 costimulation for inflationary expansion, but only on CD4 T cell help for maintenance.

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“…LCMV pMHCII-specific CD4+ memory T cells induced by acute infection also declined slowly over time 24 . Although pMHCII-specific CD4+ T cells induced by chronic viral infection were numerically stable, it is difficult to argue that these were memory cells since the relevant pMHCII was always present 25 . These results suggest that the type of stable pMHC-independent memory described for CD8+ T cells 6 is difficult if not impossible to achieve for CD4+ T cells.…”

Section: Evidence That Lineage-committed Effector Cells Become Memorymentioning

confidence: 99%

Origins of CD4+ effector and central memory T cells

2011

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Lineage-committed effector CD4+ T cells are generated at the peak of the primary response and are followed by heterogeneous populations of central and effector memory cells. Here we review the evidence that Th1 effector cells survive the contraction phase of the primary response and become effector memory cells. We discuss the applicability of this concept to the Th2, Th17, follicular helper cell, and induced regulatory T cell lineages. We also discuss how central memory cells are formed with an emphasis on the role that B cells play in this process.

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Heterogeneity among Viral Antigen-Specific CD4+ T Cells and Their De Novo Recruitment during Persistent Polyomavirus Infection

Cited by 19 publications

References 56 publications

CD4⁺T Cells: Guardians of the Phagosome

CD4⁺T Cells: Guardians of the Phagosome

MHC Class Ib-Restricted CD8 T Cells Differ in Dependence on CD4 T Cell Help and CD28 Costimulation over the Course of Mouse Polyomavirus Infection

Origins of CD4+ effector and central memory T cells

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Heterogeneity among Viral Antigen-Specific CD4+ T Cells and Their De Novo Recruitment during Persistent Polyomavirus Infection

Cited by 19 publications

References 56 publications

CD4+T Cells: Guardians of the Phagosome

CD4+T Cells: Guardians of the Phagosome

MHC Class Ib-Restricted CD8 T Cells Differ in Dependence on CD4 T Cell Help and CD28 Costimulation over the Course of Mouse Polyomavirus Infection

Origins of CD4+ effector and central memory T cells

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CD4⁺T Cells: Guardians of the Phagosome

CD4⁺T Cells: Guardians of the Phagosome