International Immunology, Vol. 16, No. 2, pp. 257-264,
February 2004
© 2004 Japanese Society for Immunology
Role of L-selectin in the development of autoimmune diabetes in non-obese diabetic mice
1 Section of Immunobiology, Yale University School of Medicine, and 2 Howard Hughes Medical Institute, New Haven, CT 06520, USA 3 Present address: Clinic Foundation for Biomedical Research, IDIPAPS, Clinic and University Hospital of Barcelona, University of Barcelona, Barcelona 08036, Spain 4 Present address: Department of Immunology, Genentech, Inc., South San Francisco, CA 94080, USA 5 Present address: Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 ITD, UK
Correspondence to: R. A. Flavell, Section of Immunobiology, Yale University School of Medicine, 310 Cedar Street, FMB 412, New Haven, CT 06520, USA. E-mail: richard.flavell{at}yale.edu
Transmitting editor: M. Feldmann
Autoimmune diabetes is characterized by an early mononuclear infiltration of pancreatic islets and later selective autoimmune destruction of insulin-producing ß cells. Lymphocyte homing receptors have been considered candidate targets to prevent autoimmune diabetes. L-selectin (CD62L) is an adhesion molecule highly expressed in naive T and B cells. It has been reported that blocking L-selectin in vivo with a specific antibody (Mel-14) partially impairs insulitis and diabetes in autoimmune diabetes-prone non-obese diabetic (NOD) mice. In the present study we aimed to elucidate whether genetic blockade of leukocyte homing into peripheral lymph nodes would prevent the development of diabetes. We backcrossed L-selectin-deficient mice onto the NOD genetic background. Surprisingly NOD/L-selectin-deficient mice exhibited unaltered islet mononuclear infiltration, timing of diabetes onset and cumulative incidence of spontaneous diabetes when compared to L-selectin-sufficient animals. CD4, CD8 T cells and B cells were present in islet infiltrates from 9-week-old L-selectin-sufficient and -deficient littermates. Moreover, total splenocytes from wild-type, heterozygous or NOD/L-selectin-deficient donor mice showed similar capability to adoptively transfer diabetes into NOD/SCID recipients. On the other hand, homing of activated, cloned insulin-specific autoaggressive CD8 T cells (TGNFC8 clone) is not affected in NOD/L-selectin-deficient recipients. We conclude that L-selectin plays a small role in the homing of autoreactive lymphocytes to regional (pancreatic) lymph nodes in NOD mice.
Keywords: CD4 T cell, CD8 T cell, insulitis, T cell priming
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