Different Roles for L3T4+ and Lyt 2+ T Cell Subsets in the Control of an Acute Herpes Simplex Virus Infection of the Skin and Nervous System

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, U.K. Rat monoclonal antibodies were used to deplete selectively Lyt 2 (cytotoxic) and L3T4 (helper) T cell populations in vivo . These antibodies produced >95% depletion of the respective T cell subset as determined by fluorescent antibody and cytofluoro-graphic analyses. Antibody-treated mice were infected in the ear pinna with herpes simplex virus (HSV) and the induction of virus-specific T cell and antibody responses were monitored during the acute infection. Lyt 2-deficient mice produced delayed hypersensitivity and HSV-specific antibodies comparable to those in untreated animals. However, major histocompatibility complex class I-restricted T cell killing was abolished. In contrast, L3T4-deficient animals failed to produce either primary delayed hypersensitivity response or specific antibodies to the virus, but cytotoxic T cells responses were induced and even augmented in comparison with infected, normal animals. This observation clearly demonstrates that Lyt 2 cytotoxic T cells can be induced in a helper T cell-deficient environment. The ability of T cell subset-deficient mice to clear infectious virus was investigated in the skin of the ear and the part of the nervous system innervating the site of infection. L3T4-deficient animals showed a markedly delayed clearance of virus from the ear and also had a more florid infection of the nervous system. However, Lyt 2-deficient mice cleared the infection in the ear normally, but a severe infection of the nervous system was still observed. The implication of these observations to the pathogenesis of this virus is discussed. Keywords: HSV, T cell populations, monoclonal antibodies Received 3 October 1986; accepted 20 November 1986.