The mechanism by which HIV-1 induces CD4+ T cell death is not known. A fundamental issue is whether HIV-1 primarily induces direct killing of infected cells or indirectly causes death of uninfected bystander cells. This question was studied using a reporter virus system in which infected cells are marked with the cell surface protein placental alkaline phosphatase (PLAP). Infection by HIV-PLAP of peripheral blood mononuclear cells (PBMCs) and T cell lines leads to rapid depletion of CD4+ T cells and induction of apoptosis. The great majority of HIV-induced T cell death in vitro involves direct loss of infected cells rather than indirect effects on uninfected bystander cells. Because of its proposed role in HIV-induced cell death, we also examined the Fas (CD95/Apo1) pathway in killing of T cells by HIV-1. Infected PBMCs or CEM cells display no increase in surface Fas relative to uninfected cells. In addition, HIV-1 kills CEM and Jurkat T cells in the presence of a caspase inhibitor that completely blocks Fas-mediated apoptosis. HIV-1 also depletes CD4+ T cells in PBMCs from patients who have a genetically defective Fas pathway. These results suggest that HIV-1 induces direct apoptosis of infected cells and kills T cells by a Fas-independent mechanism.
Skip Nav Destination
Article navigation
6 April 1998
Article|
April 06 1998
HIV-1 Directly Kills CD4+ T Cells by a Fas-independent Mechanism
Rajesh T. Gandhi,
Rajesh T. Gandhi
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Search for other works by this author on:
Benjamin K. Chen,
Benjamin K. Chen
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Search for other works by this author on:
Stephen E. Straus,
Stephen E. Straus
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Search for other works by this author on:
Janet K. Dale,
Janet K. Dale
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Search for other works by this author on:
Michael J. Lenardo,
Michael J. Lenardo
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Search for other works by this author on:
David Baltimore
David Baltimore
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Search for other works by this author on:
Rajesh T. Gandhi
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Benjamin K. Chen
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Stephen E. Straus
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Janet K. Dale
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Michael J. Lenardo
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
David Baltimore
From the *Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; the ‡Dana Farber Cancer Institute, Boston, Massachusetts 02115; §The Rockefeller University, New York 10021; the ‖Laboratory of Clinical Investigation and the ¶Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; and the **California Institute of Technology, Pasadena, California 91125
Address correspondence to David Baltimore California Institute of Technology, Pasadena, CA 91125. Phone: 626-395-6301; Fax: 626-449-9374; E-mail: [email protected]
1Abbreviations used in this paper: ALPS, autoimmune lymphoproliferative syndrome; FasL, Fas ligand; hFasL, human FasL; HXBnPLAP, PLAP-expressing HXB2; NL-PI, PLAP-expressing NL43; PLAP, placental alkaline phosphatase; TUNEL, TdT-mediated dUTP nick end labeling.
R.T. Gandhi is a recipient of a Howard Hughes Postdoctoral Research Fellowship for Physicians and a National Institutes of Health (NIH) Mentored Clinical Scientist Development Award (1 K08 AI-01443-01). B.K. Chen was supported by a Medical Scientist Training Program Award (GM07739). D. Baltimore is an American Cancer Society Research Professor and is supported at MIT by funds from the Ivan R. Cottrell Chair and grants from the NIH.
Received:
December 31 1997
Revision Received:
January 23 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (7): 1113–1122.
Article history
Received:
December 31 1997
Revision Received:
January 23 1998
Citation
Rajesh T. Gandhi, Benjamin K. Chen, Stephen E. Straus, Janet K. Dale, Michael J. Lenardo, David Baltimore; HIV-1 Directly Kills CD4+ T Cells by a Fas-independent Mechanism . J Exp Med 6 April 1998; 187 (7): 1113–1122. doi: https://doi.org/10.1084/jem.187.7.1113
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
