Tb. Oriss et al., Distinct autoreactive T cell responses to native and fragmented DNA topoisomerase I: Influence of APC type and IL-2, J IMMUNOL, 166(9), 2001, pp. 5456-5463
Systemic sclerosis (SSc) is an autoimmune connective tissue disease of unkn
own etiology in which T cell responses to various autoantigens, including D
NA topoisomerase I (Topo I), have been implicated. We investigated whether
dendritic cells, generally considered to be the most potent APCs for the in
itiation of immune responses, would present either of two forms of Topo I t
o T cells more efficiently than PBMC APCs. Using cells from healthy control
s and SSc patients, several important observations were made. First, neithe
r APC type was able to initiate T cell proliferative responses to full-leng
th native Topo I unless exogenous IL-2 was added. This is in contrast to vi
gorous T cell proliferation in response to Topo I polypeptide fragments pre
sented by either APC type. Second, T cell responses to the full-length form
of Topo I presented by dendritic cells were considerably lower than respon
ses to Ag presented by PBMC APCs. Finally, no secondary T cell responses we
re observed unless the same Ag/APC combination as that used in the primary
stimulation was maintained. These data indicate that different peptides are
generated based upon the form of the Topo I and the APC that processes it.
Taken together, these results suggest that a very specific combination of
antigenic form and APC may be involved in breaking tolerance to Topo I in t
he early stages of development of SSc.