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Alina C Boesteanu, Douglas V Dolfi, Caspian H Oliai, Annie Borowski, Peter D Katsikis, CD28 costimulation is required by effector and memory CD8+ T cells (43.2), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S36, https://doi.org/10.4049/jimmunol.178.Supp.43.2
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Abstract
CD28 costimulation is crucial for priming of CD8+ T cell responses to pathogens, however its role in the later phase of the primary and in the secondary immune responses is not clear. To dissect the role of CD28, C57Bl/6 mice were primed intranasally with influenza virus and then treated with a non-depleting blocking anti CD28 antibody at days 6 and 8 post infection. The frequency and absolute number of virus-specific CD8+ T cells were reduced in anti CD28 treated (3.9±0.4%; 1.9±0.5x105) vs. untreated mice (11.5±1.2%; 7.4±1.7 x105). We found that anti-CD28 treatment induces apoptosis of virus-specific CD8+ cells while it did not affect the number of actively dividing cells. To study the role of CD28 during secondary CD8+ T cell responses, C57Bl/6 mice were primed with flu virus strain PR8 and day 60 memory cells were transferred into C57Bl/6 or CD80−/−CD86−/− deficient mice. Mice were then rechallenged with flu virus strain X31 and 7 days post rechallenge CD80−/−CD86−/− deficient mice exhibited a reduction in virus-specific CD8+ T cells in the lung, compared to C57Bl/6 mice (1.2±0.7x106 vs. 5.8±1.1x106, respectively). Failure of memory CD8+ T cells to expand in the absence of CD28 costimulation is due to a failure to downregulate Bcl-2 and to cell cycle arrest. Thus, effector and memory CD8+ T cells require CD28 costimulation to generate optimal immune responses against pathogens.
