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

Abstract

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.

Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes.

“…Since, however, after long-term depletion of the CD4 subset, the lymphocyte population was composed of a CD8 subset and of a new subset with the phenotype CD4-CD8-(recall Fig. 2), it became necessary to also consider the possibility that the antiviral function was performed by this new subset and not, as one would anticipate from published experience (19)(20)(21)(22), by CD8' effector cells generated independently of the CD4 subset . Elimination in vitro of the CD8 subset and transfer of the resulting purified CD4-CD8-population (Fig.…”

“…Recent reports have given examples for an autonomy in vivo of the CD8 subset in viral infection models involving a depletion of the CD4 subset (19)(20)(21)(22), which implies that cooperation of CD4+ helper T lymphocytes is not essential for initiating a CD8 subset-mediated immune response. Whether such a response can last long enough to also maintain a long-term control and eosin.…”

Development and Migration of Protective CD8+ T Cells into the Nervous System following Ocular Herpes Simplex Virus-1 Infection

“…In the course of this infection, HSV-1 is detected by the immune system, resulting in a multifaceted antiviral response that controls the acute infection and limits the virus to latency in ganglia of the peripheral nervous system. In fact, after the initial viral replication and the outbreak of vesicular rash, it is the antiviral T cells that usually limit and control viral replication (6,(12)(13)(14)(15)(16). By contrast, in the absence of T cell immunity, uncontrolled viral replication typically leads to lethal encephalitis (13,15,17,18).…”

Herpes simplex virus 1 (HSV-1) for cancer treatment

“…Nevertheless, herpes simplex virus triggers strong cellular and humoral immunity. In general, cell-mediated immune responses are particularly important for viral clearance, 56,59,60 as demonstrated by immunodepletion studies, 52,61 adoptive transfer experiments 53,[62][63][64] and human clinical trials. 60 It is intriguing that recurrent HSV-1 lesions can occur in the presence of both humoral and cell-mediated immunity, although duration of recurrent lesions is typically shortened compared to the original infection.…”