The immune response and the eye. TCR alpha-chain related molecules regulate the systemic immunity to antigen...

Injection of antigen into the anterior chamber (AC) of the eye results in the induction of immune deviation in which antibody production is activated and delayed-type hypersensitivity (DTH) is inhibited. This system is termed anterior chamber associated immune deviation (ACAID) and the model is used to examine certain aspects of the immunologic privilege of the eye. Recent studies have established that following antigen presentation in the eye, an 'ACAID-inducing' signal is produced that directly enters the blood. This signal then homes to the spleen where T cells that down-regulate DTH are activated. For many antigens this 'ACAID signal' is a soluble protein released within 2 days of AC injection. Although the presence of this molecule (or molecules) has been described using several antigens, the exact nature of the soluble mediator has escaped characterization. We have further explored the nature of this signal using HSV-1-induced immune deviation. Our results show the soluble 'signal' was released by T cells that encounter antigen in the ocular microenvironment. This mediator was antigen specific, contained TCR alpha-chain (but not the TCR beta-chain) determinants and had an apparent molecular weight of 46 kDa. These results show that the release of soluble TCR alpha-chain from sites of T cell interaction within the microenvironment of the eye can regulate systemic immune responses. These results have implications for the control of immune response that might be damaging to organs such as the eye.