Thyroid-infiltrating lymphocytes spontaneously synthesize IgG class thyroid
autoantibodies while blood lymphocytes require activation to produce the s
ame autoantibodies, Surprisingly, the stimulus commonly used to induce auto
antibodies by blood lymphocytes, Pokeweed mitogen (PWM), inhibits autoantib
ody synthesis by thyroid lymphocytes, To address this dichotomy, we investi
gated the Th1:Th2 cytokine balance in relation to thyroid peroxidase (TPO)
autoantibody production in cultures of thyroid, lymph node and blood lympho
cytes, The characteristic PWM effect on TPO autoantibody production by thyr
oid and blood lymphocytes (10 day cultures) was confirmed. Cytokine measure
ments in these cultures revealed that PWM increased IFN-gamma production by
thyroid, lymph node and blood lymphocytes, However, PWM enhanced IL-4 leve
ls in lymphocytes from blood and lymph node but not in thyroid lymphocytes,
Moreover, the IL-4:IFN-gamma ratios in short- and longterm cultures were h
igher for PBMC and lymph node lymphocytes than for thyroid lymphocytes,
In summary, PWM shifts the cytokine balance towards Th2 for blood lymphocyt
es and towards Th1 for thyroid lymphocytes, The shift towards Th1 in the ta
rget organ is associated with reduced autoantibody synthesis, Our observati
ons suggest that "immune deviation" towards Th2 as a form of therapy in Gra
ves' disease could project the patient from the frying pan into the fire,