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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v29.i6.20
pages 469-486

Costimulation Signals for Memory CD8+ T Cells During Viral Infections

Priyanka A. Duttagupta
Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Drexel University College of Medicine, Philadelphia, PA
Alina C. Boesteanu
Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Drexel University College of Medicine, Philadelphia, PA
Peter D. Katsikis
Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Drexel University College of Medicine, Philadelphia, PA

ABSTRACT

Costimulation signals have been recognized as critical for optimal T-cell responses and result from important interactions between receptors on the surface of T cells and their ligands on antigen-presenting cells. Two families of receptors, the CD28 family and the tumor necrosis factor receptor (TNFR) family, have been found to be major players in providing costimulation to CD8+ T cells. Recent studies using viral infection models have highlighted the importance of CD28 costimulation signals during memory responses against viruses. Programmed death-1 (PD-1), another member of the CD28 family, may contribute to functional defects of helpless memory CD8+ T cells. Members of the TNFR family, such as CD27, 4-1BB, CD40, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and OX40, have also been implicated in the survival, generation, maintenance, and quality of virus-specific memory CD8+T cells. The delivery of costimulatory molecules such as CD28, 4-1BB, and OX40 can help boost the generation and function of virus-specific memory CD8+ T cells. The use of costimulatory molecules as adjuvants, along with viral antigens in vaccines, may facilitate the generation of effective antigen-specific memory CD8+ T-cell responses. Understanding the costimulatory requirements of memory CD8+ T cells, therefore, may lead to improved vaccines that target anti-viral CD8+ T-cell memory.


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