The role of T lymphocytes in the pathology of rheumatoid arthritis (RA
) is controversial. To some extent this has resulted from contradictor
y data, but even where specific points of fact are not in dispute, the
ir interpretation often is.(1-4) Nevertheless, the basic idea of-a pat
hological T cell response in RA receives significant support from the
work of several groups who have removed them by thoracic duct drainage
, lymphapheresis or total lymphoid irradiation (TLI). Each of these pr
ocedures ameliorates RA; in the case of TLI which induces a profound a
nd sustained decrease in CD4+ cells, the effect on synovitis was prolo
nged.(5) These observations are in line with the general assumption th
at the strong association of RA with HLA-DR molecules containing a par
ticular conserved region of amino acids implies an important role for
T cells in RA(6), since the physiological role of HLA-DR molecules is
to present antigens to T cells. In addition the association with Dw4 a
nd related alleles is strongest for the most severe and persistent for
ms of disease(7), arguing that T cells may be important not just in in
itiation of RA but also in its perpetuation. However, the infiltrating
T cells seem to be remarkably inactive and as a population to lack sp
ecificity for any particular antigen, leading some to conclude that th
eir role is either passive or irrelevant, while others contend that it
is precisely this inactivity which is responsible for the persistence
of RA.