T cell phenotypes of the normal nasal mucosa: Induction of Th2 cytokines and CCR3 expression by IL-4

Mucosal environments such as that of the nose are points of first contact b etween the human organism and its environment. At these sites the immune sy stem must be regulated to differentiate between and respond appropriately t o pathogens and harmless contaminants, T cell-driven immune responses broad ly fall into Th1- or Th2-type phenotypes, with increasing evidence that the recruitment of these T lymphocyte subsets is mediated by selective express ion of specific chemokine receptors, We have investigated the immunology of the normal nasal mucosa. We show that nasal T cell lines from normal indiv iduals, expanded by culture in IL-2, show reduced expression of the Th2-typ e cytokines IL-4 and IL-5 compared with lines derived from the blood of the same subjects. These T cells also show reduced expression of the Th2-selec tive chemokine receptor, CCR3, but similar levels of CCR4 compared with the blood-derived lines. This apparent suppression of Th2 cytokine and CCR3 ex pression by nasal T cells was reversed by addition of IL-4 to the culture m edium. These data are consistent with the presence of a nasal mucosal micro environment that suppresses Th2 responses and may represent a protective me asure against atopic allergic disease in humans and a favoring of Th1 respo nses to infectious agents. In contrast, T cell expression of CCR1 was highe r in the nose than in the blood regardless of the culture medium cytokine e nvironment in keeping with a role for this receptor in tissue homing or lym phocyte activation.