Expression and function of 4‐1BB during CD4 versus CD8 T cell responses <i>in vivo</i>

Dawicki, Wojciech; Watts, Tania H.

doi:10.1002/eji.200324278

Cited by 95 publications

(92 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[34,50,[54][55][56][57][58]. In addition, recent reports using TCR transgenic mice show a positive role of CD137 in CD4 + T cell activation in vivo [59,60]. Further work in defined in vivo systems of antigen-specific CD4 + T cells is needed to clarify these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

Arribillaga

Sarobe

Arina

et al. 2005

Vaccine

View full text Add to dashboard Cite

The induction of protective or therapeutic cellular immunity against hepatitis C virus (HCV) is a difficult goal. In a previous work we showed that immunization with a recombinant adenovirus encoding HCV-NS3 (RAdNS3) could partially protect mice from challenge with a vaccinia virus encoding HCV antigens. We sought to investigate whether systemic administration of an immunostimulatory monoclonal antibody directed against the lymphocyte surface molecule CD137 could enhance the immunity elicited by RAdNS3. It was found that treatment with anti-CD137 mAb after the administration of a suboptimal dose of RAdNS3 enhanced cytotoxic and T helper cell responses against HCV NS3. Importantly, the ability of RAdNS3 to induce protective immunity against challenge with a recombinant vaccinia virus expressing HCV proteins was markedly augmented. Thus, combination of immunostimulatory anti-CD137 mAb with recombinant adenoviruses expressing HCV proteins might be useful in strategies of immunization against HCV.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

Arribillaga

Sarobe

Arina

et al. 2005

Vaccine

View full text Add to dashboard Cite

show abstract

“…We selected the TNFR superfamily members CD27 and 4-1BB as targets, because both are known to influence the CD8 T cell response. CD27 is expressed constitutively on naive CD8 T cells, whereas 4-1BB is induced within 24 h of T cell activation in vivo (10,11). Studies using CD27 or 4-1BB ligand (4-1BBL)-deficient mice demonstrated a nonredundant contribution by both receptors to the accumulation of influenza virus-specific CD8 T cells during the primary response and the formation and response of memory cells (12,13).…”

mentioning

confidence: 99%

Differential Impact of CD27 and 4-1BB Costimulation on Effector and Memory CD8 T Cell Generation following Peptide Immunization

Willoughby

Kerr

Rogel

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

The factors that determine differentiation of naive CD8 T cells into memory cells are not well understood. A greater understanding of how memory cells are generated will inform of ways to improve vaccination strategies. In this study, we analyzed the CD8 T cell response elicited by two experimental vaccines comprising a peptide/protein Ag and an agonist that delivers a costimulatory signal via CD27 or 4-1BB. Both agonists increased expansion of Ag-specific CD8 T cells compared with Ag alone. However, their capacity to stimulate differentiation into effector and memory cells differed. CD27 agonists promoted increased expression of perforin and the generation of short-lived memory cells, whereas stimulation with 4-1BB agonists favored generation of stable memory. The memory-promoting effects of 4-1BB were independent of CD4 T cells and were the result of programing within the first 2 d of priming. Consistent with this conclusion, CD27 and 4-1BB–stimulated CD8 T cells expressed disparate amounts of IL-2, IFN-γ, CD25, CD71, and Gp49b as early as 3 d after in vivo activation. In addition, memory CD8 T cells, generated through priming with CD27 agonists, proliferated more extensively than did 4-1BB–generated memory cells, but these cells failed to persist. These data demonstrate a previously unanticipated link between the rates of homeostatic proliferation and memory cell attrition. Our study highlights a role for these receptors in skewing CD8 T cell differentiation into effector and memory cells and provides an approach to optimize vaccines that elicit CD8 T cell responses.

show abstract

“…Evidence that 4-1BB can play a role early in the response comes from systemic administration of agonist anti-4-1BB Abs, which can enhance initial antitumor and antiviral T cell responses with greater effects on CD8 compared with CD4 T cells (20 -24). However, studies in 4-1BB ligand (4-1BBL)4 -deficient mice showed that 4-1BBL was dispensable for primary responses to nonreplicating Ags or to influenza virus delivered via a minimally infectious systemic route (19,25). Under these conditions, 4-1BBL was found to control the magnitude of the recall response to influenza virus (25), later attributed to a role for 4-1BBL in maintaining CD8 T cell survival in the weeks after initial infection (26).…”

mentioning

confidence: 99%

Endogenous 4-1BB Ligand Plays a Critical Role in Protection from Influenza-Induced Disease

Lin

Sedgmen

Moraes

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

A critical issue during severe respiratory infection is whether it is the virus or the host response that does the most damage. In this study, we show that endogenous 4-1BBL plays a critical role in protecting mice from severe effects of influenza disease. During mild respiratory influenza infection in which virus is rapidly cleared, the inducible costimulatory receptor 4-1BB is only transiently induced on lung T cells and 4-1BB ligand (4-1BBL) is completely dispensable for the initial CD8 T cell response and mouse survival. In contrast, during more severe respiratory influenza infection with prolonged viral load, 4-1BB expression on lung CD8 T cells is sustained, and 4-1BBL-deficient mice show decreased CD8 T cell accumulation in the lungs, decreased viral clearance, impaired lung function, and increased mortality. Transfer of an optimal number of naive Ag-specific T cells before infection protects wild-type but not 4-1BBL-deficient mice from an otherwise lethal dose of influenza virus. T he CD8 T cells are important mediators of protective immunity to viruses (1). Indeed a strong CD8 T cell response to influenza offers the hope of cross-protective immunity to diverse influenza strains (2, 3). However, there is a concern that too strong an immune response in the lung will cause immune pathology and a worse outcome (4 -6). Upon initial encounter with Ag, T cells commit to programmed expansion, which occurs independently of the continued presence of Ag (7,8). How then does the immune system provide the appropriate level of T cell stimulation for a particular infection? T cells regulate their level of response by integrating signals from the Ag-specific receptor as well as from costimulatory, coinhibitory, and cytokine receptors which in turn influence the initiation, duration, and differentiation of the response (9 -12). The initial activation of T cells requires costimulatory signals from CD28, expressed on resting T cells. In addition, during an on-going immune response, other costimulatory receptors and ligands are up-regulated on the T cells and APCs (13-15). The question arises as to why so many costimulatory receptor ligand pairs have accumulated in the mammalian immune system. Here we provide evidence that the expression of one such costimulatory receptor, 4-1BB, is sustained in response to severe as compared with mild respiratory infection with influenza virus, thereby allowing the immune system to maintain a level of CD8 T cell response appropriate for the severity of the infection.The receptor 4-1BB (CD137) is a member of the TNFR family expressed on Ag-receptor activated T cells (14, 16 -18). In vivo with nonreplicating immunogens, 4-1BB is rapidly and transiently up-regulated on T cells upon immunization, before the first cell division and concomitantly with the expression of the early activation marker CD69 (19). Evidence that 4-1BB can play a role early in the response comes from systemic administration of agonist anti-4-1BB Abs, which can enhance initial antitumor and antiviral T cell responses wi...

show abstract

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

Cited by 95 publications

References 44 publications

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

Differential Impact of CD27 and 4-1BB Costimulation on Effector and Memory CD8 T Cell Generation following Peptide Immunization

Endogenous 4-1BB Ligand Plays a Critical Role in Protection from Influenza-Induced Disease

Contact Info

Product

Resources

About