Lymphocyte homing in xenotransplanted human thyroid tissue can be inhibited by LFA-1 and ICAM-1 antibodies.
OBJECTIVE
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, 10(6) 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.


CONCLUSIONS
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.
Department of Medicine I, Center of Internal Medicine, J.W. Goethe-University, Frankfurt, Germany. Jungheim@aol.com
K
K
Jungheim
G
G
Caspar
K H
KH
Usadel
P M
PM
Schumm-Draeger
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D040881:CD11a Antigen / Q000032:analysis; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology* / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D015703:Antigens, CD; D040881:CD11a Antigen; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1