Lymphocyte Homing in Xenotransplanted Human Thyroid Tissue Can Be Inhibited by LFA-1 and ICAM-1 Antibodies

Abstract

Objectives

: Homing of lymphocytes is an important factor with respect to the initiation of the autoimmune process in Graves' disease (GD). As previously shown, human lymphocytes, particularly of intrathyroidal origin, derived from patients with GD, are able to migrate into normal xenotransplanted thyroid tissue and induce functional and histological changes. The aim of this study was to investigate the effect of LFA-1 and ICAM-1 antibodies on the homing of lymphocytes of different origin into xenografted human thyroid tissue. Methods: Eighty-five nude mice bearing 8-week-old xenografts of normal human thyroid tissue were treated twice with anti-CD 54 (anti-ICAM-1), anti-CD 11a (anti-LFA-1), a combination of both, or, serving as controls, iso-antibodies without specific binding capacity or saline. Thereafter, intrathyroidal (ITL) or peripheral blood lymphocytes (PBL) obtained from 4 patients with GD or saline were injected into the animals (i.v., 0.2 mL, 10⁶ cells). After 48 hours the mice were sacrificed and transplants as well as mice thyroids were examined by immunohistochemical staining with Ki67, CD3, HLA-II (DAKO, Hamburg), IgG, CD44, ICAM-1, and VCAM-1 (Immunotech, Hamburg). Results: Pretreatment with anti-ICAM-1 and anti-LFA-1 decreased lymphocyte homing (CD3-staining), and expression of HLA-II, IgG, CD44, and VCAM-1 in the transplants. Conclusion: Our data show that [ICAM-1/LFA-1 stimulated (induced)] lymphocyte homing and subsequently thyrocyte proliferation are inhibited by ICAM-1 and LFA-1 antibodies in xenotransplanted thyroid tissue. This suggests that ICAM1 and LFA-1 play an important role in the early steps of autoimmune thyroid disease. The inhibition/suppression of ICAM-1 and LFA-1 interaction by respective antibodies, as demonstrated in the present study, may provide a new concept for prophylaxis and therapy.