Enrichment of immediate-early 1 (m123/pp89) peptide-specific CD8 T cells in a pulmonary CD62L(lo) memory-effector cell pool during latent murine cytomegalovirus infection of the lungs

Interstitial cytomegalovirus (CMV) pneumonia is a clinically relevant compl ication in recipients of bone marrow transplantation (BMT). Recent data for a model of experimental syngeneic BMT and concomitant infection of BALB/c mice with murine CMV (mCMV) have documented the persistence of tissue-resid ent CD8 T cells after clearance of productive infection of the lungs (J. Po dlech, R. Holtappels, M.-F. Pahl-Seibert, H.-P. Steffens, and M. J. Reddeha se, J. Virol. 74:7496-7507, 2000). It was proposed that these cells represe nt antiviral "standby" memory cells whose functional role might be to help prevent reactivation of latent virus. The pool of pulmonary CDS T cells was composed of two subsets defined by the T-cell activation marker L-selectin (CD62L): a CD62L(hi) subset of quiescent memory cells, and a CD62L(lo) sub set of recently resensitized memory-effector cells. In this study, we have continued this line of investigation by quantitating CD8 T cells specific f or the three currently published antigenic peptides of mCMV: peptide YPHFMP TNL processed from the immediate-early protein IE1 (pp89), and peptides YGP SLYRRF and AYAGLFTPL, derived from the early proteins m04 (gp34) and M84 (p 65), respectively. IE1-specific CDS T cells dominated in acute-phase pulmon ary infiltrates and were selectively enriched in latently infected lungs. N otably, most IE1-specific CD8 T cells were found to belong to the CD62L(lo) subset representing memory-effector cells. This finding is in accordance w ith the interpretation that IE1-specific CD8 T cells are frequently resensi tized during latent infection of the lungs and may thus be involved in the maintenance of mCMV latency.