γδ cells and the regulation of mucosal immune responses

We are only now uncovering the potentially important contributions made to immune responses by gamma delta cells. These contributions are likely to be particularly important at mucosal sites, where gamma delta cells are disproportionately enriched. Indeed, gamma delta cells have proven biological activity in the lung. In addition, gamma delta cells are also enriched in young rather than adult animals. Studies of mutant mice have demonstrated that alpha beta T cells are seemingly essential for high-affinity, cognate immunological memory, whereas gamma delta cells contribute to the early stages of an immune response and to the regulation of alpha beta T cell- and B cell-mediated immunity. To explore further the role of gamma delta cells in immune responses, we have investigated whether their contribution is greater during the early period of life, when the cells are more abundant. In a natural system of coccidial infection of gut epithelial cells, we find that alpha beta T cell responses are less essential for immunoprotection during primary challenge of young mice than is true for adult animals. This "ineffectiveness" creates a "window of importance" for the immunoprotective capacity of gamma delta cells, which seem thereby to be more crucial in young compared with older animals. The relative ineffectiveness of alpha beta T cells in young mice may be attributable to a bias toward Th2 activity. We therefore hypothesize that gamma delta cell activity, elicited by infection early in life, may compensate for defects in Th1 activity and may actually accelerate the bias in alpha beta T cells away from Th2. This has obvious implications for susceptibility to Th2-type allergic responses.