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 studiedin untreated and in irradiated mice. FITC-labeled cells fromspleen, lymph nodes or bone marrow of healthy or diabetic donorsdid home to the inflamed islets of unmanipulated recipients.B and T cells migrated equally well, whereas rare neutrophilsentered the islets. Lymphocyte homing was blocked by anti-L-selectinand anti-4 integrin antibodies.Insulitis transfer experimentsusing mice congenic at the Thy-1 locus showed that anti-4 integrintreatment totally inhibited the migration of donor type T cellsin the islets, whereas anti-L-selectin only had an early andtransient effect. The expression of vascular addressins in theislets was linked to the presence of mononuclear cells. Thus,in the developing islet infiltrate, the entry of cells appearscontinuous and restricted to lymphocytes, whether autoreactiveor not, and involves the L-selectin. This mechanism rather promotesthe migration of naive-type cells. Conversely,during the adoptivetransfer of insulitis the entry of L-selectin^– diabetogenicT cells is highly favored, to the detriment of L-selectin⁺ naivetype cells.