Effective immune responses to foreign antigens require cells to “traffic” through tissues. Chemokines (chemotactic cytokines) are critical mediators that provide the trafficking signals to immune cells. These are low-molecular-weight proteins, of which more than 50 have been identified to date; they have been classified into subgroups based on their amino acid sequence. Although there is some overlap in the function of these cytokine species, they can also be classified functionally into those that promote neutrophil recruitment (eg, IL-8); T helper-1 (Th1) lymphocyte recruitment and activation (macrophage inflammatory protein-1β [MIP-1β]); monocyte-macrophage recruitment (monocyte chemotactic protein-1 [MCP-1]); and eosinophil recruitment (eotaxin).
Many chemokines have been identified as playing important roles in corneal inflammation. A brief tabulation of some important soluble mediators involved in immune and inflammatory responses of the cornea and ocular surface appears in Table 6-1.
Immunoregulation of the Ocular Surface
Immunoregulation of the ocular surface occurs through tolerance and regulation of the innate and adaptive arms of the ocular immune response. The normal, uninflamed conjunctiva contains polymorphonuclear leukocytes (neutrophils); lymphocytes (including regulatory T cells [Treg cells], which dampen the immune response); macrophages; plasma cells; and mast cells. In addition, the conjunctival stroma has an endowment of dendritic antigen-presenting cells (APCs). The epithelium contains a special subpopulation of dendritic APCs known as Langerhans cells, which are capable of both antigen uptake and priming (sensitizing) of naive (antigen-inexperienced) T lymphocytes. Hence, these dendritic cells serve as the sentinel cells of the immune system of the ocular surface. In addition to containing immune cells, the conjunctiva has a plentiful supply of blood vessels and lymphatic vessels, which facilitate the trafficking of immune cells and antigens to the draining lymph nodes, where the adaptive immune response is generated. This occurs through the recruitment of Treg cells, which return to the ocular surface to modulate and suppress the local immune response (Fig 6-1).
The normal, uninflamed cornea, like the conjunctiva, is endowed with dendritic cells. Like those in the conjunctiva, the dendritic cells in the corneal epithelium are called Langerhans cells. They are located primarily in the corneal periphery and limbus. These APCs are in an activated, mature state (expressing class II major histocompatibility complex [MHC] antigens and costimulatory molecules) and hence are capable of efficiently stimulating T cells. In addition to these dendritic cells (Fig 6-2), small numbers of lymphocytes are present in the peripheral epithelium and anterior stroma of the cornea. A highly regulated process, mediated by vascular endothelial adhesion molecules and cytokines, controls the recruitment of the various leukocyte subsets from the intravascular compartment into the limbal matrix. Immune responses are also mediated by Treg cells in the regional lymph nodes and perhaps at the local level as well.