Our Science – Ohlen Website

Claes R. Ohlen, Ph.D.

AIDS and Cancer Virus Program Head, Retroviral Immunology Laboratory Senior Investigator (Contr) SAIC-Frederick, Inc. NCI-Frederick Building 535, Suite 413 Frederick, MD 21702-1201 Phone:   301-846-7601 Fax:   301-846-5588 E-Mail:   cohlen@ncifcrf.gov

Biography

Dr. Ohlen received his Ph.D. from the Karolinska Institute, Stockholm, Sweden 1992. His graduate work was focused on mouse studies of T and NK cells in tumor and transplantation models, as well as genetic and biochemical studies of antigen presentation for T cells. After a post-doc position at Oxford University, UK, in the group of Alain Townsend, Dr. Ohlen 1994 joined Phil Greenberg's group at Department of Immunology, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, as a Senior Fellow to study basic questions of T cell tolerance and autoimmunity. He joined the faculty of Department of Immunology, University of Washington, 1997 as an Acting Instructor and became Assistant Research Professor 2001. In 2005 Dr Ohlen was also appointed Assistant Director, Immunology Core, Center for AIDS Research, National Primate Research Center, University of Washington, Seattle, WA. In 2004, Dr. Ohlen was recruited to the AVP at SAIC-Frederick and joined the program in January 2005 as a Senior Scientist/Principal Investigator (PI) and Head, Retroviral Immunology Section.

Research

The overall aim for our Section is to characterize the nature and antiviral potential of T cell responses: i) study the role of T cells in controlling viral replication after vaccination; ii) critically address the potential of antigen specific T cells to control viral replication in primary infection, including evaluating their potential to prevent establishment of infection when transferred at time of challenge; and iii) analyze the cellular immune responses during acute and chronic SIV infection.
CD8+ cytotoxic T lymphocytes (CTL) play an important role in controlling the initial peak of acute viremia after HIV and SIV infection, as well as in managing the persistent viral load during the chronic phase of infection. Despite a detectable frequency of CTL specific for the virus during the chronic phase where the host is able to partially suppress and control the infection, the virus is never completely eradicated and the host therefore never cleared from infection. In the absence of drug treatment, the control of viremia during the chronic phase is eventually lost and infected individuals develop AIDS. It is not known why not all infected cells are killed by the immune system and the infection consequently never cleared, but mechanisms possibly include (i) latently infected cells hiding from the immune system through lack of viral replication, (ii) infected cells persisting in tissues where T cells normally do not traffic, (iii) mutations in the viral genome leading to viral escape from the T cells, as well as (iv) an insufficient number of virus-specific CTL limiting the viral control.
Two main questions this Section are asking are if adoptive transfer of a large number of cloned autologous virus-specific CD8+ CTL can (A) convey sterilizing immunity and provide protection from SIV infection in a naïve host, and (B) suppress the viral load in SIV infected Rhesus macaques during the chronic phase of infection.
As a means to evaluate and confirm efficacy of generated CTL clones against virus infected cells before adoptive transfer into the host, the section is also aiming at establishing an in vitro viral inhibition assay using SIV specific CD8+ T cell clones as effector cells and SIV infected autologous CD4+ positive T cell clones as target cells. This system will allow the Section to screen effector clones with different functional and cell surface phenotype in a direct assay measuring inhibition of viral spread (using flow cytometry and staining for intracellular SIV gag) and viral replication (using RT PCR to measure viral RNA in supernatants) as readout.
These studies will critically address the role of CD8+ cytotoxic T cells as potential effector mechanism when utilizing preventive or therapeutic vaccines; the immunobiology of HIV/SIV specific CTL in infected hosts; as well as lay the foundation for subsequent HIV/SIV vaccine studies using adoptive T cell transfer in macaque models.

Key collaborators include:
Dr. Daniel Douek, VRC-NIH
Dr. Francois Villinger, Emory University
Dr. Louis Giavedoni, Southwest National Primate Research Center

This page was last updated on 7/23/2008.