Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection.
CMVs are beta herpesviruses that establish lifelong latent infection of their hosts. Acute infection of C57BL/6 mice with murine CMV elicits a very broad CD8 T cell response, comprising at least 24 epitopes from 18 viral proteins. In contrast, we show here that the CD8 T cell response in chronically infected mice was dominated by only five epitopes. Altogether, four distinct CD8 T cell kinetic patterns were evident. Responses to some epitopes, including M45, which dominates the acute response, contracted sharply after day 7 and developed into stable long-term memory. The response to m139 underwent rapid expansion and contraction, followed by a phase of memory inflation, whereas the response to an M38 epitope did not display any contraction phase. Finally, responses against two epitopes encoded by the immediate early gene IE3 were readily detectable in chronically infected mice but near the limit of detection during acute infection. CD8 T cells specific for the noninflationary M45 epitope displayed a classic central memory phenotype, re-expressing the lymph node homing receptor CD62L and homeostatic cytokine receptors for IL-7 and IL-15, and produced low levels of IL-2. Responses to two inflationary epitopes, m139 and IE3, retained an effector memory surface phenotype (CD62L(low), IL-7Ralpha(-), IL-15Rbeta(-)) and were unable to produce IL-2. We suggest that immunological choices are superimposed on altered viral gene expression profiles to determine immunodominance during chronic murine CMV infection.
Munks
Michael W
MW
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Cho
Kathy S
KS
Pinto
Amelia K
AK
Sierro
Sophie
S
Klenerman
Paul
P
Hill
Ann B
AB
D016475:3T3 Cells; D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D049109:Cell Proliferation; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006566:Herpesviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017874:Immediate-Early Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D016056:Immunodominant Epitopes; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; C088646:IE3 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments