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Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;
Mathematical and Statistical Computing Laboratory, Center of Information Technology, National Institutes of Health, Bethesda, MD 20892; and
DNA Array Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224
In an attempt to understand the molecular basis for the
immunological memory response, we have used cDNA microarrays to measure
gene expression of human memory and naive CD4+ T cells at
rest and after activation. Our analysis of 54,768 cDNA clones provides
the first glimpse into gene expression patterns of memory and naive
CD4+ T cells at the genome-scale and reveals several novel
findings. First, memory and naive CD4+ T cells expressed
similar numbers of genes at rest and after activation. Second, we have
identified 14 cDNA clones that expressed higher levels of transcripts
in memory cells than in naive cells. Third, we have identified 135 (130
known genes and 5 expressed sequence tags) up-regulated and 68 (42
known genes and 26 expressed sequence tags) down-regulated cDNA clones
in memory CD4+ T after in vitro stimulation with
anti-CD3 plus anti-CD28. Interestingly, the increase in mRNA
levels of up-regulated genes was greater in memory than in naive
CD4+ T cells after in vitro stimulation and was higher with
anti-CD3 plus anti-CD28 than with anti-CD3 alone in both
memory and naive CD4+ T cells. Finally, the changes in
expression of actin and cytokine genes identified by cDNA microarrays
were confirmed by Northern and protein analyses. Together, we have
identified
200 cDNA clones whose expression levels changed after
activation and suggest that the level of expression of up-regulated
genes is a molecular mechanism that differentiates the response of
memory from naive CD4+ T cells.
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