Craig:
This topic was an area of pretty intense controversy a few years back.
The relative role of CD4 vs CD8 T-cells as well as the V-alpha or
V-beta repertoires of the synovial T-cell populations have been
studied by many different investigators -- often with conflicting
results. Although it has been a few years since I have been involved
in this area of investigation, my own feeling is that the association
of RA with particular HLA DR alleles points to the CD4 subset as
critical. My research indicated that if one looked at the synovial
T-cell population as a whole, there was no skewing of the TCR
repertoire or the CD4/CD8 ratios relative to peripheral blood.
However, if one analyzed the population of FACS sorted CD4+, CD25+
(IL-2R positive as a marker of activation), then there was typically a
marked restriction in the clonal diversity of this subpopulation. The
V-gene usage varied somewhat from person to person, but in many of the
patients I studied, the VB14 gene was used far more often in the
clones found among activated synovial CD4 cells than in the peripheral
T-cell population at large. The literature on this topic is quite
extensive (see papers by Brian Kotzin, Larry Steinman, or Mark Howell
for examples). Hope this is of use to you.
D.G. Spinella, Ph.D.
