Following ocular infection of normal mice, herpes simplex virus type 1 (HSV-I) establishes a latent infection in the trigeminal ganglia (TG) with the complete absence of detectable infectious virus. In this study, the role of CD4(+) and CD8(+) T cell dependent immune responses is examined in relation to cleaving infectious virus from the TG following HSV-I ocular challenge. Nude mice, which lack T cells, and MHCo/o mice, which lack both MHC class I and MHC class ii, were challenged ocularly with wild-type HSV-1. Over 70% of the TG from mice surviving the infection contained infectious virus, indicative of a chronic infection in these TG, rather than a latent infection. No infectious virus was detected in TGs from infected C57BL/6 parental mice. Ocular challenge of CD4(o/o) A(beta)(o/o), CD8(o/o) or beta(2)m(o/o) mice resulted in latent rather than chronic infection. Similarly, when C57BL/6 mice were depleted for CD4(+) or CD8(+) T cells from 4 days before ocular challenge to 26 days after ocular challenge, no free virus was detected in TGs of challenged mice. In contrast, when mice were depleted of both their CD4(+) and CD8(+) T cells, over 90% of TGs were positive for free virus, suggesting that the tack of virus clearance was due to the combined lack of both CD4(+) T cells and CD8(+) T cells (i.e. in the presence of either CD4(+) T cells or CD8(+) T cells alone all of the infectious virus was cleared and latency was established). (C) 1999 Academic Press.