Homing of lymphocytes into islets of Langerhans in prediabetic non-obese diabetic mice is not restricted to autoreactive T cells.
Non-obese diabetic mice spontaneously develop a type 1 diabetes. The entry of leukocytes in the islets of Langerhans was studied in untreated and in irradiated mice. FITC-labeled cells from spleen, lymph nodes or bone marrow of healthy or diabetic donors did home to the inflamed islets of unmanipulated recipients. B and T cells migrated equally well, whereas rare neutrophils entered the islets. Lymphocyte homing was blocked by anti-L-selectin and anti-alpha 4 integrin antibodies. Insulitis transfer experiments using mice congenic at the Thy-1 locus showed that anti-alpha 4 integrin treatment totally inhibited the migration of donor type T cells in the islets, whereas anti-L-selectin only had an early and transient effect. The expression of vascular addressins in the islets was linked to the presence of mononuclear cells. Thus, in the developing islet infiltrate, the entry of cells appears continuous and restricted to lymphocytes, whether autoreactive or not, and involves the L-selectin. This mechanism rather promotes the migration of naive-type cells. Conversely, during the adoptive transfer of insulitis the entry of L-selectin- diabetogenic T cells is highly favored, to the detriment of L-selectin+ naive type cells.
Faveeuw
C
C
CNRS URA 1461, Hôpital Necker, Paris, France.
Gagnerault
M C
MC
Kraal
G
G
Lepault
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000528:radiation effects; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology*; D005260:Female; D016219:Immunotherapy, Adoptive; D039441:Integrin alpha4; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D007700:Kinetics; D019041:L-Selectin / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011236:Prediabetic State / Q000276:immunology* / Q000473:pathology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019041:L-Selectin; D039441:Integrin alpha4