Immunization with different viral antigens alters the pattern of T cell exhaustion and latency in herpes simplex virus type 1-infected mice.
We have shown previously that immunization with herpes simplex virus type 1 (HSV-1) glycoprotein K (gK) exacerbated corneal scarring (CS) in ocularly infected mice. In this study, we investigated whether higher levels of CS were correlated with higher levels of latency and T cell exhaustion in gK-immunized mice. BALB/c mice were vaccinated with baculovirus-expressed gK or gD or mock immunized. Twenty-one days after the third immunization, mice were ocularly infected with 2 × 10(4) PFU/eye of virulent HSV-1 strain McKrae. On day 5 postinfection, virus replication in the eye was measured, and on day 30 postinfection, infiltration of the trigeminal ganglia (TG) by CD4, CD8, programmed death 1 (PD-1), and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) was monitored by immunohistochemistry and quantitative real-time PCR (qRT-PCR). This study demonstrated that higher levels of CS were correlated with higher levels of latency, and this was associated with the presence of significantly higher numbers of CD4(+)PD-1(+) and CD8(+)PD-1(+) cells in the TG of the gK-immunized group than in both the gD- and mock-immunized groups. Levels of exhaustion associated with Tim-3 were the same among gK- and mock-vaccinated groups but higher than levels in the gD-vaccinated group. In this study, we have shown for the first time that both PD-1 and Tim-3 contribute to T cell exhaustion and an increase of latency in the TG of latently infected mice.
Allen
Sariah J
SJ
Center for Neurobiology and Vaccine Development, Ophthalmology Research Laboratories, Department of Surgery, CSMC Burns & Allen Research Institute, Los Angeles, California 90048, USA.
Mott
Kevin R
KR
Zandian
Mandana
M
Ghiasi
Homayon
H
D000704:Analysis of Variance; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002921:Cicatrix / Q000473:pathology / Q000821:virology*; D003315:Cornea / Q000473:pathology / Q000821:virology*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D000072597:Hepatitis A Virus Cellular Receptor 2; D006561:Herpes Simplex / Q000276:immunology* / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007114:Immunization / Q000009:adverse effects*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D061026:Programmed Cell Death 1 Receptor; D011991:Receptors, Virus / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000378:metabolism; D014764:Viral Proteins / Q000008:administration & dosage / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
D000943:Antigens, Differentiation; D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; D017931:DNA Primers; D018076:DNA, Complementary; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011991:Receptors, Virus; C072448:UL53 protein, Human herpesvirus 1; D014764:Viral Proteins