CD4+ T lymphocytes with constitutive CD40 ligand in preautoimmune (NZB x NZW)F1 lupus-prone mice: phenotype and possible role in autoreactivity.
Lupus disease is marked by B lymphocyte hyperactivity and the production of Abs to dsDNA. The production of these anti-dsDNA Abs is T lymphocyte dependent. However, it is not clear how CD4+ T lymphocytes provide help for B lymphocytes to produce IgG anti-dsDNA Abs. One possible mechanism is suggested by studies showing that human patients with systemic lupus erythematosus and lupus mice have increased numbers of CD40 ligand (CD40L)+ T and B lymphocytes. The results described in this study reveal that young, clinically healthy lupus-prone New Zealand Black x New Zealand White F1 (BWF1) mice have naive CD4+ T cells with preformed CD40L. These cells contribute to a brisk response to immunization and to the production of anti-dsDNA Abs. In vitro experiments revealed that CD4+ T cells with preformed CD40L could, upon stimulation, provide antiapoptotic signals for B cells but could not induce proliferation or reduce activation threshold. These results suggest that the direct target cells for the effect of T cells with preformed CD40L in lupus may not be B lymphocytes.
Lettesjö
H
H
The Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom.
Burd
G P
GP
Mageed
R A
RA
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000097:blood; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D023201:CD40 Ligand / Q000096:biosynthesis / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003433:Crosses, Genetic; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007114:Immunization; D016130:Immunophenotyping; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008808:Mice, Inbred CBA; D008814:Mice, Inbred NZB; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000974:Antibodies, Antinuclear; D000941:Antigens; D023201:CD40 Ligand; D004247:DNA