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No, RA or RO are not sufficient to distinguish memory from naive T cells (in
humans). In fact, using RA and RO together doesn't work either. There are
RA+RO- memory cells in both CD4 and CD8 lineages. (I really hope people will
stop using the CD4/RA/RO and CD8/RA/RO combinations to distinguish naive and
memory T cells, and move onto the better combinations listed below). If anyone
disagrees, EMail me directly--I will be happy to provide proof (after ISAC) in
the way of published and unpublished figures. Or find me at ISAC!
For CD4, the CD45RA+ memory cells are rare in healthy people, but can become
quite prevalent in, for instance, HIV-infected adults. In HIV, these cells can
show an "activated" phenotype (38+ DR+). They are RO-.
For CD8, RA+ memory cells are reasonably frequent (between 5-30% of CD8) in
healthy adults. The CD8+ RA+ cells constitute a majority of the CD57+ (and
CD28-) CD8 T cells.
The RA+ memory cells can be distinguished from RA+ naive cells on the basis of
CD62L expression (the memory cells are CD62L-; naive are CD62L+).
Alternatively, naive cells express dim levels of CD11a (memory cells are bright
for CD11a). However, this distinction may not be as easy to make.
To summarize: to uniquely identify naive vs. memory cells, you need to use at
least three color: {CD4 or CD8} plus CD45RA plus {CD62L or CD11a}. The best
would be to use a fourth color with CD3 to aid in identifying the T cell
lineage.
Note that "RA-" cells really aren't truly negative--they do express some RA.
For the CD8's, they actually express quite a bit. Therefore, you cannot use CD3
alone plus RA and CD62L, because the "RA-" CD8 cells can express as much RA as
do the CD4 naive (RA+) cells! Therefore, CD3 plus CD45RA is the worst possible
way you could try to distinguish memory and naive (it fails miserably).
By the way, in PBMC, CD45R0 and RA have essentially identical abilities to
distinguish these subsets: all RA+ cells are RO- and vice versa. When you
activate T cells, however, many can become double-positive (bright) for both RA
and RO.
mr
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