PURPOSE. Stromal keratitis is an immunopathologic consequence of herpes sim
plex virus (HSV) infection of the cornea. The lesion is immunopathologic, b
ut the identities of molecules that drive the reaction remain unresolved. T
o exclude viral antigen recognition as a necessary step in the disease proc
ess, ocular HSV infection was followed in Tg-RAG mice (OVA-TCR transgenic m
ice crossed to RAG2-deficient mice) whose limited T-cell repertoire did not
include immune responsiveness to HSV.
METHODS. Mice with T-cell specificity to OVA peptide (Tg-RAG mice) as well
as control DO11.10 and BALB/c mice were infected with HSV on the scarified
cornea and subjected to clinical, histologic, and immunologic analysis. To
evaluate involvement of OVA-specific CD4(+) T cells in lesion development i
n Tg-RAG mice, monoclonal antibody to CD4(+) T cells was used for in vivo C
D4(+) T-cell depletion.
RESULTS. Tg-RAG mice were capable of eliciting ocular lesions in the absenc
e of detectable reactivity to viral antigens. Lesion manifestation in Tg-RA
G mice mas CD4(+) T-cell dependent and the cellular infiltrates and their i
nflammatory products in the HSV-infected cornea were comparable to similarl
y infected BALB/c and DO11.10 mice.
CONCLUSIONS. The authors conclude that mechanisms other than viral antigen
recognition, and hence molecular mimicry, are at play and are sufficient to
cause HSV-induced stromal keratitis. The data imply a significant role for
non-virus-specific CD4(+) T cells that could become activated by an inflam
matory milieu consisting of enhanced accessory molecules and proinflammator
y cytokines in the cornea.