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 journalArticlepeer-review

36 Scopus citations


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
Issue number6
StatePublished - Sep 15 1996

ASJC Scopus subject areas

  • Immunology


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