The Natural History of Disease Expression in CD4 and CD8 Gene-Deleted New Zealand Black (NZB) Mice

Shao Yuan Chen, Yuichi Takeoka, Aftab A. Ansari, Richard Boyd, Dennis M. Klinman, M. Eric Gershwin

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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 immunologie 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 MTS 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 immunologie 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-γ 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.

Original languageEnglish (US)
Pages (from-to)2676-2684
Number of pages9
JournalJournal of Immunology
Volume157
Issue number6
StatePublished - Sep 15 1996

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New Zealand
Cell Lineage
Genes
Autoantibodies
Erythrocytes
Cytokines
Thymocytes
Interleukin-4
Staining and Labeling
Messenger RNA
DNA

ASJC Scopus subject areas

  • Immunology

Cite this

Chen, S. Y., Takeoka, Y., Ansari, A. A., Boyd, R., Klinman, D. M., & Gershwin, M. E. (1996). The Natural History of Disease Expression in CD4 and CD8 Gene-Deleted New Zealand Black (NZB) Mice. Journal of Immunology, 157(6), 2676-2684.

The Natural History of Disease Expression in CD4 and CD8 Gene-Deleted New Zealand Black (NZB) Mice. / Chen, Shao Yuan; Takeoka, Yuichi; Ansari, Aftab A.; Boyd, Richard; Klinman, Dennis M.; Gershwin, M. Eric.

In: Journal of Immunology, Vol. 157, No. 6, 15.09.1996, p. 2676-2684.

Research output: Contribution to journalArticle

Chen, SY, Takeoka, Y, Ansari, AA, Boyd, R, Klinman, DM & Gershwin, ME 1996, 'The Natural History of Disease Expression in CD4 and CD8 Gene-Deleted New Zealand Black (NZB) Mice', Journal of Immunology, vol. 157, no. 6, pp. 2676-2684.
Chen, Shao Yuan ; Takeoka, Yuichi ; Ansari, Aftab A. ; Boyd, Richard ; Klinman, Dennis M. ; Gershwin, M. Eric. / The Natural History of Disease Expression in CD4 and CD8 Gene-Deleted New Zealand Black (NZB) Mice. In: Journal of Immunology. 1996 ; Vol. 157, No. 6. pp. 2676-2684.
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