Human CD4-Major Histocompatibility Complex Class II (DQw6) Transgenic Mice in an Endogenous CD4/CD8-deficient Background: Reconstitution of Phenotype and Human-restricted Function

Rae S.M. Yeung, Josef M. Penninger, Thomas M. Kündig, Yuk Law, Ken Yamamoto, N. Kamikawaji, Linda Burkly, Takehiko Sasazuki, Richard Flavell, Pamela S. Ohashi, Tak W. Mak

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Abstract

To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/−), after homologous recombination, have been generated. We report that expression of human CD4 molecule in mCD4/8-/− mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs. Upon vesicular stomatitis virus (VSV) challenge, the reconstituted mature T cell population effectively provide T help to B cells in immunoglobulin class switching from IgM to specific IgG-neutralizing antibodies. Human CD4+ DQw6+ double transgenic mice are tolerant to DQw6 and the DQw6 molecule functions in antigen presentation, effectively generating a human MHC class II-restricted T cell response to streptococcal M6C2 peptide. These data show that both the hCD4 and DQw6 molecules are functional in mCD4/8-/− mice, fully and stably reconstituting this limb of the human immune system in mice. This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS).

Original languageEnglish
Pages (from-to)1911-1920
Number of pages10
JournalJournal of Experimental Medicine
Volume180
Issue number5
DOIs
Publication statusPublished - Nov 1 1994

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Yeung, R. S. M., Penninger, J. M., Kündig, T. M., Law, Y., Yamamoto, K., Kamikawaji, N., Burkly, L., Sasazuki, T., Flavell, R., Ohashi, P. S., & Mak, T. W. (1994). Human CD4-Major Histocompatibility Complex Class II (DQw6) Transgenic Mice in an Endogenous CD4/CD8-deficient Background: Reconstitution of Phenotype and Human-restricted Function. Journal of Experimental Medicine, 180(5), 1911-1920. https://doi.org/10.1084/jem.180.5.1911