Leidos Biomedical Research, Inc.
Frederick National Laboratory for Cancer Research
Frederick, MD 21702-1201
Claes Ohlen received his Ph.D. from the Karolinska Institute, Stockholm, Sweden
1992. His graduate work 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, 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 2001 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 AIDS and Cancer
Virus Program at SAIC/Frederick National Laboratory for Cancer Research and joined the program in January 2005 as a
Senior Scientist/Principal Investigator (PI) and Head, Retroviral Immunology Section.
The overall goal for our laboratory is a better understanding of antiviral T cell
responses and their potential for control of primate lentiviral infection, seeking
improved prevention and treatment of AIDS virus infection using a rhesus macaque
Control of HIV and SIV infection by adaptive immune responses is considered to be
mediated by both antibodies and CD8+ T cells. Studies of passive transfer of neutralizing
antibodies have shown that humoral responses are capable of mediating protection
from infection. However, because the breadth and titers of neutralizing antibodies
required for protection are considerably higher than achieved by current vaccine
protocols, much interest and effort during recent years has focused on T cell based
vaccines. Understanding the nature of effective antiviral T cell responses remains
an important objective, but despite much effort, the nature and mechanism(s) of
protective T cell responses against primate lentiviruses remain obscure. T cells
are implicated in viral control by studies demonstrating correlations between cellular
responses and control of viral replication, studies on viral escape in T cell epitopes,
and studies involving in vivo depletion of CD8+ lymphocytes. However, these data
only indirectly implicate T cell responses in such control, and do not define the
nature of the cells or effector mechanisms responsible.
To address the role of CD8+ T cells in viral control, our laboratory is pursuing
a program of both in vitro and in vivo studies of T cell mediated virus suppression.
Our in vivo macaque studies involve various approaches based on adoptive transfer
of ex vivo-expanded SIV specific autologous T cells, and their ability to provide
protection from acute infection. The in vivo studies have generated a number of
critical questions regarding homing, persistence and mechanism of viral suppression
by T cells. We address these basic questions in vitro because they are important
and unresolved immunological issues in their own right, but also because the research
supports our in vivo effort by identifying cells to use in adoptive transfer experiments.
The system allows us to screen effector clones with different functional and cell
surface phenotype, 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.
We also study the mechanism(s) behind the clonal differences in SIV susceptibility
of CD4+ T cells generated from individual animals that we have observed, with the
aim to discover new mechanisms for virus resistance, potentially leading to novel
These studies address the role of SIV specific T cells in protection against AIDS
virus, and the immunobiology of HIV/SIV infection.