Waller Edward C P, McKinney Nicola, Hicks Ray, Carmichael Andrew J, Sissons J G Patrick, Wills Mark R
Department of Medicine, University of Cambridge Clinical School, Cambridge, UK.
Blood. 2007 Dec 15;110(13):4360-6. doi: 10.1182/blood-2007-07-104604. Epub 2007 Sep 18.
In healthy carriers of human cytomegalovirus (HCMV), the virus-specific memory CD8(+) T-cell population is often dominated by CD28(-) CD45RA(hi) cells that exhibit direct ex vivo cytotoxicity but whose capacity for proliferation and generation of further memory cells has been questioned. We show that when highly purified CD28(-) CD45RA(hi) CD8(+) T cells are stimulated with viral peptide presented by autologous monocytes, the virus-specific T cells show early up-regulation of CD137 (4-1BB) and CD278 (ICOS), re-express CD28, and proliferate with similarly high cloning efficiency in limiting dilution analysis as CD28(+) CD45RO(hi) cells or CD28(-) CD45RO(hi) cells. Using peptide-pulsed autologous fibroblasts transfected with individual costimulatory ligands as antigen presenting cells, we showed CD137L to be a key costimulatory ligand for proliferation of CD28(-) CD45RA(hi) CD8(+) T cells and not CD80, CD86, or CD275 (ICOSL). Therefore, CD28(-) CD45RA(hi) CD8(+) T cells were not terminally differentiated but required a specific costimulatory signal for proliferation.
在人类巨细胞病毒（HCMV）的健康携带者中，病毒特异性记忆性CD8(+) T细胞群体通常由CD28(-) CD45RA(hi)细胞主导，这些细胞在体外表现出直接的细胞毒性，但其增殖能力和产生更多记忆细胞的能力一直受到质疑。我们发现，当用自体单核细胞呈递的病毒肽刺激高度纯化的CD28(-) CD45RA(hi) CD8(+) T细胞时，病毒特异性T细胞会早期上调CD137（4-1BB）和CD278（ICOS），重新表达CD28，并且在有限稀释分析中与CD28(+) CD45RO(hi)细胞或CD28(-) CD45RO(hi)细胞一样具有高克隆效率地增殖。使用转染了单个共刺激配体的肽脉冲自体成纤维细胞作为抗原呈递细胞，我们发现CD137L是CD28(-) CD45RA(hi) CD8(+) T细胞增殖的关键共刺激配体，而不是CD80、CD86或CD275（ICOSL）。因此，CD28(-) CD45RA(hi) CD8(+) T细胞并非终末分化，而是需要特定的共刺激信号来进行增殖。
