Herpes Simplex Virus-Specific CD8+ T Cells Can Clear Established Lytic Infections from Skin and Nerves and Can Partially Limit the Early Spread of Virus after Cutaneous Inoculation

Abstract

HSV infects skin or mucosal epithelium as well as entering the sensory nerves and ganglia. We have used TCR-transgenic T cells specific for the immunodominant class I-restricted determinant from HSV glycoprotein B (gB) combined with a flank zosteriform model of infection to examine the ability of CD8+ T cells to deal with infection. During the course of zosteriform disease, virus rapidly spreads from the primary inoculation site in the skin to sensory dorsal root ganglia and subsequently reappears in the distal flank. Virus begins to be cleared from all sites about 5 days after infection when gB-specific CD8+ T cells first appear within infected tissues. Although activated gB-specific effectors can partially limit virus egress from the skin, they do so only at the earliest times after infection and are ineffective at halting the progression of zosteriform disease once virus has left the inoculation site. In contrast, these same T cells can completely clear ongoing lytic replication if transferred into infected immunocompromised RAG-1−/− mice. Therefore, we propose that the role of CD8+ T cells during the normal course of disease is to clear replicating virus after infection is well established rather than limit the initial spread of HSV from the primary site of inoculation.

Cutting Edge: Prolonged Antigen Presentation after Herpes Simplex Virus-1 Skin Infection

“…Inoculation by flank scarification is described in detail elsewhere (9,10). At specified times after HSV-1 flank infection, the inoculation site or the corresponding area on the contralateral flank was excised from anesthetized mice by cutting out a 0.5 ϫ 0.5-cm 2 area of full-thickness skin surrounding the site.…”

Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation

“…KOS.LβA was generated by recombining SC16LβA (31) with the KOS strain by transfecting vero cells with a mixture of SC16.LβA and KOS DNA and selecting plaque-purified nonneurovirulent recombinants. Epicutaneous infection by scarification was carried out by using 1 × 10 6 pfu HSV (KOS, K.L8A, or KOS.LβΑ) as described (32). Intravaginal infection was performed on progesterone-treated mice (Depo Provera, 2 mg per mouse).…”

“…The level of infectious virus was determined within homogenized skin or in vaginal fluids by pfu assays as described (32). Vaginal fluids were collected by using calcium alginate swabs.…”

Cutting Edge: Local Recall Responses by Memory T Cells Newly Recruited to Peripheral Nonlymphoid Tissues

“…Mice were infected with 1 ϫ 10 6 PFU of HSV-1 via flank scarification as previously described (10). Dorsal root ganglia (DRGs) (T8 -T12) harvested from naive donor mice or mice infected with HSV-1 Ͼ20 days earlier were harvested and grafted beneath the kidney capsule of syngeneic recipient mice (9).…”

“…The method for in vitro activation of CD8 ϩ T cells has previously been described (10). C57BL/6 donor mice received 10 7 in vitro activated OT-I.CD45.1 and gBT-I.CD45.1 cells via i.v.…”