Th1 and Th17 in tumor Immunity versus autoimmunity (128.15)

Abstract

Abstract To determine the role of Th1 and Th17 T cells in the reactivity to self antigens in tumor vs autoimmunity, IFN-γ and IL17 secreting T cells to rat neu and mouse thyroglobulin (mTg) were measured in neu transgenic BALB/c (NeuT) and NeuTxDR3 mice, which expressed neu and HLA-DR3. HLA-DR3 is associated with susceptibility to some autoimmune diseases in humans and experimental autoimmune thyroiditis (EAT) in mice. BALB/c and BALBxDR3 served as controls. α-neu response was induced by vaccination with pneuTM encoding neu ECD and TM & pGM-CSF, or by TC-1/neu, heterologous tumor cells transfected with neu, and LPS. α-mTg response was induced by mTg & LPS, i.v. Regulatory T cells (Treg) were depleted by CD25 mAb 9 d before mTg. In BALBxDR3 & NeuTxDR3 mice, pneuTM & pGM-CSF vaccination induced 59 & 1 ug/ml Ab and 592 & 217 IFN-γ secreting cells. Vaccination with TC-1/neu & LPS induced 18 & 41 ug/ml neu Ab and 241 & 187 IFN-γ cells. Neu+ tumors can be regressed, yet no IL-17 was detected in any group. In BALBxDR3 mice depleted of Treg and immunized with mTg/LPS, 51400 U/ml mTg Ab, 119 IFN-γ secreting cells, and 64 IL-17 secreting cells were present, with 40–60% thyroid destruction. Hence, Th1 but not Th17 were activated by neu vaccination in normal or NeuT mice. Both Th1 and Th17 were activated in mTg-induced EAT. Since Neu vaccination & LPS did not induce IL-17 secretion, Th17 activation is unrelated to LPS. Elucidating the precise roles for Th1 and Th17 in tumor immunity and thyroiditis is critical when both are present in an individual. (CA 125680, CA76340, DK45960, St. John Hosp)