J. Buer et al., INTERLEUKIN-10 SECRETION AND IMPAIRED EFFECTOR FUNCTION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-RESTRICTED T-CELLS ANERGIZED IN-VIVO, The Journal of experimental medicine, 187(2), 1998, pp. 177-183
Continuous antigenic stimulation in vivo can result in the generation
of so-called ''anergic'' CD4(+) or CD8(+) T cells that fail to prolife
rate upon antigenic stimulation and fail to develop cytolytic effector
functions. Here we show that class II major histocompatibility comple
x-restricted T cells specific for influenza hemagglutinin (HA) that be
come allergic in mice expressing HA under control of the immunoglobuli
n kappa promoter exhibit an impaired effector function in causing diab
etes in vivo, as compared to their naive counterparts, when transferre
d into immunodeficient recipients expressing HA under the control of t
he insulin promoter. Furthermore, HA-specific T cells anergized in viv
o contain higher levels of interleukin (IL)-4 RNA (mRNA) than naive an
d recently activated T cells with the same specificity and more than a
100-fold higher levels of IL-10 mRNA. The higher expression of the IL
-10 gene is also evident at the protein level. These findings raise th
e interesting possibility that T cells rendered anergic in vivo have i
n fact become regulatory T cells that may influence neighboring immune
responses through the release of IL-10.