B R Ksander — Page 3 | PubMed Health

PubMed1987

Cell-mediated immune tolerance to HSV-1 antigens associated with reduced susceptibility to HSV-1 corneal lesions.

We have investigated the involvement of cell-mediated immune responses to Herpes simplex virus type 1 (HSV-1) in the pathogenesis of HSV-1 induced corneal stromal lesions in mice. Topical corneal (TC) HSV-1 infection induced a vigorous delayed hypersensitivity response, as well as lymphoproliferative and cytotoxic responses in the regional lymph nodes. The cytotoxic response involved HSV-1 specific and genetically restricted cytotoxic T lymphocytes, and activated natural killer cells. Half of the TC HSV-1 infected mice developed corneal stromal inflammation and scarring, the cause of visual morbidity in human herpetic disease. However, injection of HSV-1 into the ocular anterior chamber (AC) prior to, or simultaneously with, TC HSV-1 infection resulted in a profound state of cell-mediated immune tolerance of HSV-1 antigens. The tolerance was characterized by a substantial reduction in delayed hypersensitivity, lymphoproliferative, and cytotoxic responses to HSV-1 and was associated with virtually complete protection from corneal stromal lesions induced by HSV-1. These findings suggest a pathogenetic role for cell-mediated immunity and indicate the feasibility of preventing stromal disease through proper manipulation of the immune response.

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Inhibition of lymphocyte proliferation by aqueous humor.

Antigens introduced into the anterior chamber (AC) of the eye elicit systemic, antigen-specific suppression of delayed hypersensitivity combined with primed cytotoxic T cells and elevated levels of serum antibodies, a unique immune response termed anterior chamber associated immune deviation (ACAID). Among the mechanisms that have been implicated in the induction of this response is the possibility that T cells first recognize antigen within the AC, where-upon they then escape to initiate the induction of systemic suppression. Because this possibility implies that T-cell recognition of antigen could occur in the aqueous humor (AqH) that normally fills the AC, we tested the effects of freshly obtained AqH on lymphocyte proliferative responses in vitro. The results indicate that AqH from mice and rabbits profoundly inhibits (1) T-lymphocyte proliferation to antigens, (2) T- and B-lymphocyte responses to polyclonal mitogens, and (3) growth-factor-driven lymphocyte proliferation. The antiproliferative activity of AqH was also effective on some, but not all, neoplastic cells. The activity was shown to be neither species specific nor directly cytotoxic to cells. The activity was distinct from the growth inhibitory effects of normal mouse serum. We conclude that AqH contains a soluble factor(s) that is a potent inhibitor of cell proliferation. The potential role(s) of this activity in ocular wound healing and in intraocular immune responses are discussed.

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