Generation of CD8+ T Cell Memory in Response to Low, High, and Excessive Levels of Epitope

Wherry, E. John; McElhaugh, Michael; Eisenlohr, Laurence C.

doi:10.4049/jimmunol.168.9.4455

Cited by 89 publications

(78 citation statements)

References 31 publications

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“…We find similar correlations between infection dose and population sizes in the CD8 + T cell compartment (Fig. 5B), as reported previously by others [22,23]. Thus, it seems unlikely that differences in antigen load requirements cause the different re-expansion characteristics of CD4 + and CD8 + Listeria-specific effector T cells.…”

Section: In Vivo Expansion Of Antigen-specific Cd4 + and Cd8 + Memorysupporting

confidence: 90%

Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations

et al. 2003

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Our knowledge about the kinetics and dynamics of complex pathogen-specific CD8 + T cell responses and the in vivo development of CD8 + memory T cells has increased substantially over the past years; in comparison, relatively little is known about the CD4 + T cell compartment. We monitored and directly compared the phenotypical changes of pathogen (Listeria monocytogenes)-specific CD8 + and CD4 + T cell responses under conditions leading to effective and long-lasting protective immunity. We found that the general kinetics of bacteriaspecific CD8 + and CD4 + T cells during the effector and post-effector phases are synchronized. However, later during the memory phase, CD8 + and CD4 + T cell populations differ substantially. Whereas CD8 + memory T cell populations with immediate effector function are readily detectable in lymphoid and non-lymphoid tissues and remain remarkably stable in size, antigen-specific CD4 + effector-memory T cells decline continuously in frequency over time. These findings have important implications for the better understanding of the in vivo development of protective immunity towards intracellular pathogens.

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Section: In Vivo Expansion Of Antigen-specific Cd4 + and Cd8 + Memorysupporting

confidence: 90%

Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations

et al. 2003

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“…Thus, it was shown that at least two distinct subpopulations of CD4 + T-cells develop after resolution of experimental L. (L.) major infection, but only one requires the presence of the parasite (Wherry et al 2002, Gollob et al 2005. In humans, it is difficult to determine whether or not long life immunity is dependent on the persistence of parasite in tissues, since they are frequently exposed to new infections in endemic areas.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have addressed the requirements for generation of CD8 + memory cells (Hamann et al 1999, Wherry et al 2002, but little is known about the establishment of long lived CD4 + T-cells (Gollob et al 2005). Thus, it was shown that at least two distinct subpopulations of CD4 + T-cells develop after resolution of experimental L. (L.) major infection, but only one requires the presence of the parasite (Wherry et al 2002, Gollob et al 2005.…”

Section: Discussionmentioning

confidence: 99%

T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

Bittar

Nogueira

Vieira-Gonçalves

et al. 2007

Mem. Inst. Oswaldo Cruz

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Subclinical or asymptomatic infection is documented in individuals living in endemic areas for leishmaniasis suggesting that the development of an appropriate immune response can control parasite replication and maintain tissue integrity. A low morbidity indicates that intrinsic factors could favor resistance to Leishmania infection. Herein, leishmanial T-cell responses induced in subjects with low susceptibility to leishmaniasis as asymptomatic subjects were compared to those observed in cured cutaneous leishmaniasis (CCL) patients, who controlled the disease after antimonial therapy. All of them have shown maintenance of specific long-term immune responses characterized by expansion of higher proportions of CD4 + as compared to CD8 + Leishmania reactive T-lymphocytes. Asymptomatic subjects had lower indexes of in vitro Leishmania induced lymphoproliferative responses and interferon-gamma (IFN-γ) production in comparison to CCL patients. On the other hand, interleukin (IL-10) production was much higher in asymptomatics than in CCL, while no differences in IL-5 levels were found. In conclusion, long lived T-cell responses achieved by asymptomatic individuals differed from those who had developed symptomatic leishmaniasis in terms of intensity of lymphocyte activation (proliferation or IFN-γ) and regulatory mechanisms (IL-10). The absence of the disease in asymptomatics could be explained by their intrinsic ability to create a balance between immunoregulatory (IL-10) and effector cytokines (IFN-γ), leading to parasite destruction without producing skin tissue damage. The establishment of profiles of cell-mediated immune responses associated with resistance against Leishmania infection is likely to make new inroads into understanding the long-lived immune protection against the disease.Key words: asymptomatic infection -Leishmania (Viannia) braziliensis -cured leishmaniasis -cytokines -T-cell subsetslong term immunity (Grimaldi Jr & MacMahon-Pratt 1991). The spectrum of the clinical presentation ranges from self-healing or benign cutaneous lesions to more severe forms, such as disseminated lesions or mucosal involvement (Da-Cruz & Pirmez 2005).Studies conducted in mice and humans have unequivocally shown that a major T-cell driven component underlies the establishment of acquired immunity and protection against re-infection ( Coutinho et al. 1996, Louis et al. 1998, Bosque et al. 2000. Cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factoralpha (TNF-α) activate macrophages for killing parasites, while interleukin (IL)-4, IL-5, IL-10, and transforming grow factor-beta (TGF-β) favor intracellular parasite growth (Louis et al. 1998. In addition, IL-10 production by CD4 + CD25 + T-cells is required for maintenance of Leishmania after cure, which in turn preserves an adaptive immunity to L. (Leishmania) major (Belkaid et al. 2002).The majority of ATL patients develop cutaneous leishmaniasis (CL) (Oliveira-Neto et al. 2000), but occurrence of subclinical or asymptomatic infection strongly suggests that po...

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“…In primary infection, the amount of Ag determines the size of the murine CD8 ϩ T cell response. Subsequently, the magnitude of this CD8 ϩ T cell response sets the size of the Ag-specific T cell pool during the memory phase (35,36). Recently, it was demonstrated that the contraction phase of the primary immune response is independent of the clearance of Ag (37).…”

Section: Discussionmentioning

confidence: 99%

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

Gamadia

Leeuwen

Remmerswaal³

et al. 2004

The Journal of Immunology

108

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Based on the expression of the TNFR SFP CD27, two Ag-primed CD8+ T cell subsets can be discerned in the circulation of healthy individuals: CD27+ T cells that produce a variety of cytokines but do not display immediate cytolytic activity; and cytotoxic CD27− T cells, which secrete only IFN-γ and TNF-α. The mechanism that controls the generation of these different phenotypes is unknown. We show that CMV reactivation not only increases the number of virus-specific T cells but also induces their transition from a CD27+ to a CD27− phenotype. In support of a relation between pool size and phenotype in a cohort of latently infected individuals, the number of Ag-specific CD27− CD8+ T cells was found to be linearly related to the total number of CMV-specific CD8+ T cells. In vitro studies revealed that the acquisition of the CD27− phenotype on CMV-specific T cells depended on the interaction of CD27 with its cellular ligand, CD70. Expression of CD70 was proportional to the amount of antigenic stimulation and blocked by the CD4+ T cell-derived cytokine IL-21. Thus, induction of CD70, which may vary in distinct viral infections, appears to be a key factor in determining the size and phenotype of the CMV-specific T cell population in latently infected individuals.

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Generation of CD8+ T Cell Memory in Response to Low, High, and Excessive Levels of Epitope

Cited by 89 publications

References 31 publications

Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations

Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations

T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

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Generation of CD8+ T Cell Memory in Response to Low, High, and Excessive Levels of Epitope

Cited by 89 publications

References 31 publications

Differences in maintenance of CD8+ and CD4+ bacteria‐specific effector‐memory T cell populations

Differences in maintenance of CD8+ and CD4+ bacteria‐specific effector‐memory T cell populations

T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

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Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations

Differences in maintenance of CD8⁺ and CD4⁺ bacteria‐specific effector‐memory T cell populations