I wanted to add to Jose's outstanding review of CD4+CD8+ ("DP") T
cells in peripheral blood. The level of CD8 expression (as well as
exactly the form, be it CD8 alpha/alpha or CD8 alpha/beta)
distinguishes different kinds of "DP" cells. As we showed in Blood
in 1997 [Watanabe et al], there are subsets of CD8dull CD4+ T cells
(that express CD8a/a homodimers) which can become prevalent in
certain diseases (such as late-stage AIDS, after chemotherapy), but
can be found in variable proportions in healthy adults. These cells
are unlikely to be CD4 cells that have upregulated CD8alpha, but
rather constitute a distinct lineage (because we can identify
differentiation & effector stages within the CD4+CD8dull, and have
determined the VBeta repertoire of the "naive" CD4+CD8-dull to be
very different from that of either CD4+ or CD8+ single-positive T
cells--and yes, I know that doesn't prove they're a distinct lineage,
but we can have that argument over a nice bottle of wine at ISAC).
In any case, there are also CD4+CD8+ which express CD8alpha/beta
heterodimers are are "bright" CD8. (These distinctions only work
well if you are using very bright CD8 reagents that have low
backgrounds). These "true" double positives are very rare, and
usually are a consequence of having dead cells: dead cells are
notoriously sticky. We showed that, especially after stimulation,
90% of "CD4+CD8+" cells are actually dead cells and could have nearly
any original phenotype. However, there are very rare "true" DP cells
that are not dead. Whether these are a distinct lineage of mature T
cell or whether they cells that have perhaps "spilled out" of the
thymus during development is not known to me.
Note that reports of CD4+CD8+ T cells making IL4 must be taken with a
grain of salt, because these are certainly dead cells. When
excluding dead cells after stimulation (by, e.g., EMA staining), the
few remaining true DP cells do not make IL4. Certain antibodies to
IL4 have a very high propensity to bind dead cells--although I
believe the particular clone we used that had this property has been
discontinued.
The finding of CD4+CD8+ in primates is likely not an artefact of dead
cells--there's simply too many to be explained by death. However, we
still need to determine if these cells are CD8-dull (i.e., CD8a/a) or
CD8-bright (and express CD8a/b heterodimers). This is important
because the CD8-dull cells (which can be either CD4+ or CD4-,
incidentally) are a very different "lineage" than the DP.
mr
This archive was generated by hypermail 2b29 : Sat Mar 10 2001 - 19:31:16 EST