Prevention of lymphadenopathy in MRL-lpr/lpr mice by blocking peripheral lymph node homing with Mel-14 in vivo.
MRL-lpr/lpr mice develop massive lymphadenopathy and autoimmunity. There is evidence that both migration and local proliferation contribute to the accumulation of Ly-2-, L3T4-, 6B2+ T cells in the peripheral lymph node (PLN). Mel-14 is an antibody which binds to the lymphocyte lymph node homing receptor (gp90Mel-14) and can block migration of lymphocytes to the PLN. Treatment of mice from birth to 11 wk of age with Mel-14 and another rat IgG2a mAb, 6B2, resulted in reduction (10- to 20-fold) in lymphadenopathy. Mel-14, but not 6B2, preferentially reduced the percentages of Thy-1+, 6B2+ lymphocytes in the lymph node. Treatment with a third antibody, anti-Ly-1, had no effect on lymphadenopathy. Mel-14 treatment resulted in diversion of the Ly-2-, L3T4-, 6B2+, gp90Mel-14 cells to the spleen and consequently induced marked splenomegaly. Thymocytes from MRL-lpr/lpr and MRL-+/+ mice were analyzed by two-color flow cytometry analysis after depletion of Ly-2+ and L3T4+ T cells. There was no difference in the percent of Ly-2-, L3T4-, 6B2+, gp90Mel-14 positive thymocytes comparing these two strains. Mel-14 treatment did not alter Ig levels or autoantibody production. These studies suggest Mel-14 reduced lymphadenopathy by interfering with homing to PLN, whereas 6B2 may have interfered with marrow production of precursor cells or killed 6B2+ cells after they exited the marrow. The data are consistent with the idea that lymphadenopathy occurs in MRL-lpr/lpr mice due to increased homing gp90-Mel-14 T cells to the PLN and that gp90Mel-14 is a necessary receptor for the abnormal 6B2+ T cells.
Mountz
J D
JD
Cellular Immunology Section, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda 20892.
Gause
W C
WC
Finkelman
F D
FD
Steinberg
A D
AD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000502:physiology; D007119:Immunoblastic Lymphadenopathy / Q000517:prevention & control*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000145:classification / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing; D013154:Spleen / Q000166:cytology; D013163:Splenomegaly
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing