The natural history of disease expression in CD4 and CD8 gene-deleted New Zealand black (NZB) mice.
CD4 and CD8 gene-deleted New Zealand black (NZB) mice and, as controls, B6.CD4 -/-, B6.CD8 -/-, NZB, and B6 wild-type (wt) mice were studied for phenotypic and immunologic parameters to determine the contribution of CD4 and CD8 cell lineages in NZB mice. These studies suggest surprisingly that a number of abnormalities are not due to either CD4+ or CD8+ cell lineages but rather are most likely due to non-CD4+ and -CD8+ cell lineages and/or background genes. Such abnormalities include altered thymic architecture, decreased staining of MITS 33+ medullary thymocytes, and an increased frequency of splenic IgM secretory cells. In contrast, deletion of either CD4+ or CD8+ cells appears to differentially influence immunologic function. Deletion of CD8+ cells did not influence titers of spontaneously occurring anti-erythrocyte or anti-DNA autoantibodies. interestingly, 50% of NZB.CD4 -/- mice contained levels of anti-erythrocyte IgG and anti-ssDNA IgM autoantibodies; even without detectable CD4+ cells. Such deletion of CD4+ cells, while leading to marked decreases in the prototype cytokines that characterize Th1 and Th2 subsets in B6 mice, led to a marked increase in IFN-gamma and a moderate increase in IL-4 mRNA levels in NZB.CD4 -/- mice. These data suggest that whereas non-CD4+ and -CD8+ cell lineages and NZB background genes have a marked influence in the development of autoimmune abnormalities, CD4+ cells appear to play a major role in influencing the cytokine environment, whereas CD8+ cells appear to play a minor role.
Chen
S Y
SY
Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California at Davis 95616, USA.
Takeoka
Y
Y
Ansari
A A
AA
Boyd
R
R
Klinman
D M
DM
Gershwin
M E
ME
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics / Q000503:physiopathology*; D015704:CD4 Antigens / Q000235:genetics*; D016827:CD8 Antigens / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D017353:Gene Deletion; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D013950:Thymus Gland / Q000098:blood supply / Q000473:pathology
D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M