International Immunology Advance Access published online on October 30, 2009
International Immunology, doi:10.1093/intimm/dxp107
On the role of the inhibitory receptor LAG-3 in acute and chronic LCMV infection
Institute of Microbiology, Department of Biology, Wolfgang-Pauli-Strasse 10, HCI G401, ETH Zurich, 8093 Zurich, Switzerland
Correspondence to: Correspondence to: A. Oxenius; E-mail: oxenius{at}micro.biol.ethz.ch
Chronic viral infections are often characterized by CD8 T-cell responses with poor cytokine secretion potential and limited expansion of the CD8 T-cell pool, collectively referred to as CD8 T-cell exhaustion. Exhaustion of lymphocytic choriomeningitis virus (LCMV)-specific CD8 T cells was shown to be partially regulated by the inhibitory receptor programmed death 1 (PD-1). Here, we demonstrate that exhausted LCMV-specific CD8 T cells also express the negative regulatory receptor lymphocyte activation gene 3 (LAG-3) which is mainly expressed on cells co-expressing the negative regulatory receptors PD-1 and Tim-3. Expression levels of LAG-3 on anti-viral CD8 T cells remain stable over short-term in vitro stimulations in presence of antigenic peptide. Nevertheless, in vitro and in vivo blockade of LAG-3 did not rescue cytokine production by virus-specific CD8 T cells and did not alter the virus titer in various organs. Likewise, chronic LCMV infection of LAG-3–/– mice led to a comparable degree of T-cell exhaustion as observed in C57BL/6 controls and to similar virus titers. Further, LAG-3 did not influence T-cell activation or cell division during chronic LCMV infection. These data suggest that even though LAG-3 is continuously up-regulated on LCMV-specific exhausted CD8 T cells, it alone does not significantly contribute to T-cell exhaustion.
Keywords: CD8 T cell, chronic viral infection, dysfunction, inhibitory receptor
Transmitting editor: P. Ohashi
Received 19 August 2009, accepted 2 October 2009.