T-cell receptor V beta repertoire of L3T4+ regulatory T cells in anti-L3T4 antibody-induced tolerant NOD mice.
In ongoing studies, we have found that short-term administration of anti-L3T4 monoclonal antibodies (mAb) prevents the development of overt diabetes in non-obese diabetic (NOD) mice. In the present work, we asked whether L3T4+ T cells or Lyt-2+ T cells can suppress the diabetes in these mice. L3T4+ T cells or Lyt-2+ T cells were sorted using a magnetic cell sorter, then were transferred into cyclophosphamide-induced male NOD mice. We obtained evidence that the L3T4+ but not Lyt-2+ T cells did inhibit the diabetes, thereby indicating that the former can regulate diabetes in anti-L3T4 mAb-induced tolerant NOD mice. Further analysis on T-cell receptor (TCR) V beta genes on splenic T cells from anti-L3T4 mAb-treated NOD mice revealed that V beta 4-positive T cells expanded predominantly, while L3T4+ T cells represented heterogeneity of the TCR V beta gene, hence, V beta 4-positive Lyt-2+ T cells generate predominantly. Our findings suggest that both L3T4+ and Lyt-2+ T cells renew and function as regulatory cells, through clonotypic interaction in tolerant NOD mice.
Sakamoto
A
A
Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Furukawa
M
M
Iwamoto
I
I
Koike
T
T
Tomioka
H
H
Sumida
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003520:Cyclophosphamide; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000235:genetics; D005260:Female; D007108:Immune Tolerance; D007135:Immunoglobulin Variable Region / Q000235:genetics; D018189:Immunomagnetic Separation; D007518:Isoantibodies / Q000276:immunology; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000637:transplantation
D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D007518:Isoantibodies; C029805:Lyt antibodies; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003520:Cyclophosphamide