Priming of CD8+ T cells during central nervous system infection with a murine coronavirus is strain dependent.
Virus-specific CD8(+) T cells are critical for protection against neurotropic coronaviruses; however, central nervous system (CNS) infection with the recombinant JHM (RJHM) strain of mouse hepatitis virus (MHV) elicits a weak CD8(+) T-cell response in the brain and causes lethal encephalomyelitis. An adoptive transfer model was used to elucidate the kinetics of CD8(+) T-cell priming during CNS infection with RJHM as well as with two MHV strains that induce a robust CD8(+) T-cell response (RA59 and SJHM/RA59, a recombinant A59 virus expressing the JHM spike). While RA59 and SJHM/RA59 infections resulted in CD8(+) T-cell priming within the first 2 days postinfection, RJHM infection did not lead to proliferation of naïve CD8(+) T cells. While all three viruses replicated efficiently in the brain, only RA59 and SJHM/RA59 replicated to appreciable levels in the cervical lymph nodes (CLN), the site of T-cell priming during acute CNS infection. RJHM was unable to suppress the CD8(+) T-cell response elicited by RA59 in mice simultaneously infected with both strains, suggesting that RJHM does not cause generalized immunosuppression. RJHM was also unable to elicit a secondary CD8(+) T-cell response in the brain following peripheral immunization against a viral epitope. Notably, the weak CD8(+) T-cell response elicited by RJHM was unique to CNS infection, since peripheral inoculation induced a robust CD8(+) T-cell response in the spleen. These findings suggest that the failure of RJHM to prime a robust CD8(+) T-cell response during CNS infection is likely due to its failure to replicate in the CLN.
MacNamara
Katherine C
KC
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA.
Bender
Susan J
SJ
Chua
Ming Ming
MM
Watson
Richard
R
Weiss
Susan R
SR
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D018352:Coronavirus Infections / Q000276:immunology*; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D006517:Murine hepatitis virus / Q000276:immunology*; D013045:Species Specificity