Differential expression of lymphocyte homing receptors by human memory/effector T cells in pulmonary versus cutaneous immune effector sites

Abstract

The heterogeneous expression of lymphocyte homing receptors (HR) by the (CD45RA^low/RO^high) memory/effector T cell population in the human is thought to define subsets with tissue‐selective recirculatory potential. To investigate further the localization characteristics of these T cells, we used multiparameter flow cytometry to quantitate T cell subsets defined by expression of the skin‐selective HR called the cutaneous lymphocyte‐associated antigen (CLA), the peripheral lymph node (PLN) HR L‐selectin, the mucosal‐associated HR α4β7‐integrin, and the mucosal‐associated adhesion molecule αeβ7‐integrin in either cutaneous or pulmonary immune effector sites and corresponding peripheral blood. Compared to peripheral blood, skin T cells were highly enriched for the CLA⁺/L‐selectin⁺/αeβ7‐integrin⁻ memory/effector subset, whereas lung memory/effector T cells were predominantly CLA^{−to low} L‐selectin⁻, and almost half were αeβ7‐integrin⁺. α4β7‐integrin expressing memory/effector T cells were diminished in both skin and lung, suggesting that this HR is not a major participant in determining localization specificity in either of these sites. The characteristic pulmonary T cell HR phenotype did not significantly differ between the normal subjects and those with pulmonary inflammatory disease, and did not correlate with markers of T cell activation. Induction of a rapid up‐regulation of pulmonary inflammation via intrabronchial allergen challenge in asthmatic patients tended to decrease localization specificity, resulting in a more general importation of memory/effector subsets. Taken together, these results suggest that tissue microenvironments play a major role in determining the character of local T cell infiltrates via their ability to import and retain memory/effector subsets selectively or, more generally, depending on the intensity of local inflammatory stimuli.