A major aim in immunology has been to understand how the immune system evokes characteristic responses to infection, foreign tissue grafts and tumours. The current view of immunoregulation is based mainly on studies of lymphocyte subsets, either in vitro or by adoptive transfer to irradiated recipients. Many reagents are available for defining T-cell subsets, but only recently have there been helper T-cell-specific antibodies against the mouse equivalent of the Leu3/T4 (man) and W3/25 (rat) antigens. It is clear that monoclonal antibodies will eventually replace antilymphocyte globulin for immunosuppression in organ grafting, but although there has been some clinical success, most monoclonal reagents cause only transient reductions in their target cells in vivo. This uncertainty in the potency of monoclonal antibodies has led some workers to consider them as targeting agents for such highly cytotoxic drugs as ricin A (ref. 21). We show here that unmodified monoclonal antibodies can be extremely effective at depleting cells in vivo and can be used for the selective manipulation of different aspects of the immune response.

SUMMARYRat 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 cytofluorographic 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 cell 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.

Apolipoprotein E (APOE) alleles have been associated with the severity of, or susceptibility to, infection by various microbes. We investigated the potential association between the APOE-epsilon 4 allele and the rate of recurrence of genital herpes in patients who were HIV positive and herpes simplex virus type 2 (HSV-2) seropositive. The APOE-epsilon 4 allele was significantly associated with recurrent genital ulceration independent of ethnicity, antiretroviral therapy and CD4 count (OR 8.3; 95% CI 2.4 to 28.5). To our knowledge, this is the first published study to demonstrate this association and suggests that APOE-epsilon 4 may represent a future prognostic marker for symptomatic recurrence of genital herpes in individuals with HIV.

No abstract