Deficiency of CD11b or CD11d results in reduced staphylococcal enterotoxin-induced T cell response and T cell phenotypic changes.

  • Wu H
  • Rodgers J
  • Perrard X
 et al. 
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Abstract

The beta(2) integrin CD11a is involved in T cell-APC interactions, but the roles of CD11b, CD11c, and CD11d in such interactions have not been examined. To evaluate the roles of each CD11/CD18 integrin in T cell-APC interactions, we tested the ability of splenocytes of CD11-knockout (KO) mice to respond to staphylococcal enterotoxins (SEs), a commonly used superantigen. The defect in T cell proliferation with SEA was more severe in splenocytes from mice deficient in CD18, CD11b, or CD11d than in CD11a-deficient splenocytes, with a normal response in CD11c-deficient splenocytes. Mixing experiments showed that the defect of both CD11b-KO and CD11d-KO splenocytes was, unexpectedly, in T cells rather than in APC. Cytometric analysis failed to detect CD11b or CD11d on resting or activated T cells or on thymocytes of wild-type adult mice, nor did Abs directed to these integrins block responses in culture, suggesting that T cells educated in CD11b-KO or CD11d-KO mice were phenotypically altered. Consistent with this hypothesis, T cells from CD11b-KO and CD11d-KO splenocytes exhibited reduced intensity of CD3 and CD28 expression and decreased ratios of CD4/CD8 cells, and CD4(+) T cells were reduced among CD11b-KO and CD11d-KO thymocytes. CD11b and CD11d were coexpressed on a subset of early wild-type fetal thymocytes. We postulate that transient thymocyte expression of both CD11b and CD11d is nonredundantly required for normal thymocyte and T cell development, leading to phenotypic changes in T cells that result in the reduced response to SE stimulation.

Author-supplied keywords

  • Animals
  • Antigens, CD11
  • Antigens, CD11: analysis
  • Antigens, CD11: physiology
  • Antigens, CD11b
  • Antigens, CD11b: analysis
  • Antigens, CD11b: physiology
  • Antigens, CD18
  • Antigens, CD18: physiology
  • Cytotoxicity, Immunologic
  • Enterotoxins
  • Enterotoxins: immunology
  • Flow Cytometry
  • Immunophenotyping
  • Integrin alpha Chains
  • Integrin alpha Chains: analysis
  • Integrin alpha Chains: physiology
  • Ionomycin
  • Ionomycin: pharmacology
  • Killer Cells, Natural
  • Killer Cells, Natural: immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Superantigens
  • Superantigens: immunology
  • T-Lymphocytes
  • T-Lymphocytes: immunology
  • Tetradecanoylphorbol Acetate
  • Tetradecanoylphorbol Acetate: pharmacology

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Authors

  • Huaizhu Wu

  • John R Rodgers

  • Xiao-Yuan Dai Perrard

  • Jerry L Perrard

  • Joseph E Prince

  • Yasunori Abe

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