The CD4 Molecule on CD8+T Lymphocytes Directly Enhances the Immune Response to Viral and Cellular Antigens

CD8+T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8+T cells induces de novo expression of the CD4 molecule and that ligation of CD4 on this cell type modulates CD8+T cell activity in vi...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 102; no. 10; pp. 3794 - 3799
Main Authors:	Kitchen, Scott G., Whitmire, Jason K., Jones, Nicole R., Galic, Zoran, Christina M. R. Kitchen, Ahmed, Rafi, Zack, Jerome A., Chisari, Francis V.
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 08-03-2005 National Acad Sciences
Subjects:	Animals Antigens Antivirals Biological Sciences CD4 Antigens - physiology CD8-Positive T-Lymphocytes - immunology Cells, Cultured HLA Antigens - immunology Immune response Immune system Infections Interferon-gamma - biosynthesis Isoantigens - immunology Ligation Lymphocytic choriomeningitis virus - immunology Mice Mice, Inbred C57BL Mice, SCID Mice, Transgenic Microbiology Molecules Rodents Spleen T lymphocytes Viruses
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Summary:	CD8+T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8+T cells induces de novo expression of the CD4 molecule and that ligation of CD4 on this cell type modulates CD8+T cell activity in vitro. Herein, we investigate how the CD4 molecule expressed on murine CD8+T cells contributes to CD8+cell responses in vivo by employing adoptive transfer of CD8 cells from CD4 knockout mice into severe combined immunodeficient (SCID) recipients. Transfer of these cells into syngeneic SCID mice resulted in a decreased immune response to infection by lymphocytic choriomeningitis virus. These decreased responses occurred even in the presence of CD4+T cells, indicating that this was truly a CD8-cell defect. Similarly, transfer of CD8+T cells incapable of expressing CD4 into allogeneic SCID mice resulted in a decreased response to alloantigens compared with that of normal CD8+T cells. Therefore, CD4 expression on CD8 T lymphocytes modulates cytotoxic T lymphocyte function and is critical in vivo for optimal cell-mediated immunity to viral and alloantigens.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Abbreviations: APC, antigen-presenting cell; CTL, cytotoxic T lymphocyte; LCMV, lymphocytic choriomeningitis virus; pfu, plaque-forming units; SCID, severe combined immunodeficient; TCR, T cell receptor; Th, T helper. To whom correspondence should be addressed at: UCLA AIDS Institute, David Geffen School of Medicine, University of California, 10833 Le Conte Avenue, 11-934 Factor Building, Los Angeles, CA 90095. E-mail: jzack@ucla.edu. Author contributions: S.G.K., J.K.W., R.A., and J.A.Z. designed research; S.G.K., J.K.W., N.R.J., and Z.G. performed research; S.G.K., J.K.W., and C.M.R.K. analyzed data; and S.G.K. and J.A.Z. wrote the paper. This paper was submitted directly (Track II) to the PNAS office. Edited by Francis V. Chisari, The Scripps Research Institute, La Jolla, CA
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0406603102