Attenuation of autoimmune disease and lymphocyte accumulation in MRL/lpr mice by treatment with anti-V beta 8 antibodies.
MRL-MP-lpr/lpr mice are afflicted by a severe systemic autoimmune disease that is aggravated by the lpr mutation resulting in the accumulation of phenotypically abnormal lpr cells (CD3+CD4-CD8-) in all lymphoid issues including hyperplastic lymph nodes. Given that products of the T cell receptor V beta 8 gene family are overrepresented among lpr cells, different schedules aimed at selectively decreasing the frequency of lpr cells were designed. First, continuous administration of the monoclonal antibody F23.1 (specific for V beta 8 products) resulted in a significant depletion of V beta 8+ cells and prevented the manifestation of lymph accumulation at the same time as it reduced the serological, clinical, and histopathological signs of autoimmune disease. Along the same line, administration of either F23.1 or two different anti-F23.1 anti-idiotypic antibodies to MRL/Mp-lpr/lpr mothers elicited, in the offspring, the production of antibodies sharing a recurrent idiotype with F23.1 and resulted in long-term amelioration of autoimmunity and lymphadenopathy. Thus, a strategy aimed at specifically reducing the frequency of a subset of lpr cells proved successful in mitigating the autoimmune process.
de Alborán
I M
IM
Centro de Biología Molecular (CSIC), Universidad Autónoma, Madrid, Spain.
Gonzalo
J A
JA
Kroemer
G
G
Leonardo
E
E
Marcos
M A
MA
Martínez
C
C
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000517:prevention & control*; D005260:Female; D007116:Immunization, Passive; D008214:Lymphocytes / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000517:prevention & control*; D051379:Mice; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D014616:Vaccinia virus / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta