Differential Control of Autoantibodies and Lymphoproliferation by Fas Ligand Expression on CD4+ and CD8+ T Cells In Vivo

We have previously shown that the gld autoimmune syndrome is suppressed in lethally irradiated gld mice reconstituted with a mixture of normal and gld bone marrow (BM). Furthermore, in vivo depletion of normal Thy-1+ cells restores lymphoproliferation and autoantibody production in such chimeras, su...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-09, Vol.163 (6), p.3138-3142
Main Authors: Maldonado, Michael A, MacDonald, Glen C, Kakkanaiah, Vellalore N, Fecho, Karamarie, Dransfield, Mark, Sekiguchi, Debora, Cohen, Philip L, Eisenberg, Robert A
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Autoantibodies - biosynthesis
Autoantibodies - blood
Autoantibodies - genetics
Autoimmune Diseases - genetics
Autoimmune Diseases - immunology
Autoimmune Diseases - prevention & control
Bone Marrow Transplantation
CD4-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - metabolism
Fas Ligand Protein
Lymphocyte Activation - genetics
Lymphocyte Activation - immunology
Membrane Glycoproteins - biosynthesis
Mice
Mice, Congenic
Mice, Inbred C57BL
Mice, Knockout
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Regulatory - immunology
Transplantation Chimera
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Summary:We have previously shown that the gld autoimmune syndrome is suppressed in lethally irradiated gld mice reconstituted with a mixture of normal and gld bone marrow (BM). Furthermore, in vivo depletion of normal Thy-1+ cells restores lymphoproliferation and autoantibody production in such chimeras, suggesting that T cells bearing Fas ligand are responsible for correcting the gld defect. In this study, mixed-BM chimeras lacking either normal CD4+ (B6CD4KO-B6gld) or normal CD8+ T cells (B6CD8KO-B6gld) were generated to determine the contribution of the normal T cell subsets to disease suppression. Lymphoproliferation was completely suppressed in B6CD4KO-B6gld chimeras but only modestly in B6CD8KO-B6gld chimeras. On the other hand, both types of mixed-BM chimeras had incomplete effects on the suppression of serum autoantibodies when compared with B6gld reconstituted with isologous BM. These results suggest that both T cell subsets provide Fas ligand to suppress immune cells responsible for autoantibody production; however, CD8+ T cells are mainly responsible for preventing lymphoproliferation.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.163.6.3138