Identification of an evolutionarily conserved transcriptional signature of CD8 memory differentiation that is shared by T and B cells.

J Immunol

After Ag encounter, naive lymphocytes differentiate into populations of memory cells that share a common set of functions including faster response to Ag re-exposure and the ability to self-renew. However, memory lymphocytes in different lymphocyte lineages are functionally and phenotypically diverse. It is not known whether discrete populations of T and B cells use similar transcriptional programs during differentiation into the memory state. We used cross-species genomic analysis to examine the pattern of genes up-regulated during the differentiation of naive lymphocytes into memory cells in multiple populations of human CD4, CD8, and B cell lymphocytes as well as two mouse models of memory development. We identified and validated a signature of genes that was up-regulated in memory cells compared with naive cells in both human and mouse CD8 memory differentiation, suggesting marked evolutionary conservation of this transcriptional program. Surprisingly, this conserved CD8 differentiation signature was also up-regulated during memory differentiation in CD4 and B cell lineages. To validate the biologic significance of this signature, we showed that alterations in this signature of genes could distinguish between functional and exhausted CD8 T cells from a mouse model of chronic viral infection. Finally, we generated genome-wide microarray data from tetramer-sorted human T cells and showed profound differences in this differentiation signature between T cells specific for HIV and those specific for influenza. Thus, our data suggest that in addition to lineage-specific differentiation programs, T and B lymphocytes use a common transcriptional program during memory development that is disrupted in chronic viral infection.

Year of Publication
J Immunol
Date Published
2008 Aug 01
PubMed ID
PubMed Central ID
Grant list
K08 HL72750 / HL / NHLBI NIH HHS / United States
R01 HL082945 / HL / NHLBI NIH HHS / United States
K08 HL072750 / HL / NHLBI NIH HHS / United States
Howard Hughes Medical Institute / United States
U19 CA100265 / CA / NCI NIH HHS / United States
R01HL82945 / HL / NHLBI NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
R01 AI030914 / AI / NIAID NIH HHS / United States