CD8 T cells mediate transient herpes stromal keratitis in CD4-deficient mice.
OBJECTIVE
To evaluate the role of CD4(+) T cells in the development of murine herpes stromal keratitis (HSK).


METHODS
The corneas of wild-type (WT) BALB/c mice and three types of CD4-deficient BALB/c mice (CD4(-/-), CD4-depleted, CD4 and CD8 double-depleted) were infected with different doses of HSV-1 RE, and HSK incidence and severity were monitored. Corneal infiltrates were quantitatively and functionally assayed by flow cytometric analysis of individually digested diseased corneas and documented histologically.


RESULTS
At a relatively high infectious dose (1 x 10(5) pfu/cornea): (1) CD4-deficient and WT BALB/c mice had severe HSK with a similar incidence (80%-100%), whereas HSK did not develop in mice deficient in both CD4(+) and CD8(+) T cells; (2) neutrophils were the predominate leukocyte in the corneas of CD4-deficient and WT mice; (3) the corneas of WT mice had activated, HSV-1-specific CD4(+) T cells, but few if any CD8(+) T cells; (4) the corneas of CD4-deficient mice had activated, HSV-1-specific CD8(+) T cells; and (5) HSK in CD4-deficient mice was transient, showing loss of CD8(+) T cells at 2 to 3 weeks after infection (pi) followed by a loss of neutrophils. At a relatively low infectious dose of HSV-1 (10(3) pfu/cornea) severe HSK developed in 80% to 90% of WT mice, but in only 30% to 40% of CD4-deficient mice.


CONCLUSIONS
CD4(+) T cells preferentially mediate HSK, but, in their absence, a high infectious dose of HSV-1 can induce histologically similar but transient HSK that is mediated by CD8(+) T cells.
Lepisto
Andrew J
AJ
Department of Immunology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.
Frank
Gregory M
GM
Xu
Min
M
Stuart
Patrick M
PM
Hendricks
Robert L
RL
D000818:Animals; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D003319:Corneal Stroma / Q000821:virology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
D007371:Interferon-gamma