IL-2 production in human memory CD8+ T cells depends on ERK1 expression (150.7)

Autor: Tae Kon Kim, Cara Benjamin, Qing Ma, Wieder Eric, Krishna Komanduri
Rok vydání: 2011
Předmět:
Zdroj: The Journal of Immunology. 186:150.7-150.7
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.186.supp.150.7
Popis: Recently, we showed that human late memory (CD45RA+CD27-) CD8+ T cells have a unique cytokine signature characterized by the lack of IL-2 production, and no IL-2/IFNγ co-production. Prior studies have suggested the importance of ERK1/2, in IL-2 production; however, little is known about the individual contributions of ERK isoforms to the functional signatures of human T cell subsets. We developed flow cytometric methods to study the differential expression of ERK1 and ERK2 in CD8+ T cell maturation subsets in association with their cytokine signatures. We found that the expression of total ERK1, but not ERK2 nor Ras/Raf/MEK1/MEK2, are diminished by ~80% (measured by flow cytometry and western blotting) in late memory CD8+ T cells, in comparison to early memory CD8+ T cells. Consequently, the diminished expression of total ERK1 resulted in decreased total and phosphorylated ERK1/2. In addition, total ERK1 expression in CD8+ T cells was bimodal on flow cytometry (ERK1high and ERK1low) and consistently identified the subset of memory CD8+ T cells capable (ERK1high) or incapable of IL-2 production (ERK1low) (mean IL-2 production in ERK1high vs. in ERK1low: 20% vs. 1.5%, (n=9, p=0.0039)). Interestingly, late memory cells transduced with lentivirus-expressing ERK1 cDNA, produced 2.5 times more IL-2 than control (n=3, p
Databáze: OpenAIRE