Differential expression of lymphocyte homing receptors by human memory/effector T cells in pulmonary versus cutaneous immune effector sites.
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 alpha 4 beta 7-integrin, and the mucosal-associated adhesion molecule alpha e beta 7-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+/alpha e beta 7-integrin- memory/effector subset, whereas lung memory/effector T cells were predominantly CLA-to low L-selectin-, and almost half were alpha e beta 7-integrin+. alpha 4 beta 7-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.
Picker
L J
LJ
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072.
Martin
R J
RJ
Trumble
A
A
Newman
L S
LS
Collins
P A
PA
Bergstresser
P R
PR
Leung
D Y
DY
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016023:Integrins / Q000096:biosynthesis; D019041:L-Selectin; D017493:Leukocyte Common Antigens; D008168:Lung / Q000276:immunology*; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D015815:Cell Adhesion Molecules; D016023:Integrins; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7; C070709:integrin alphaEbeta7; D019041:L-Selectin; D017493:Leukocyte Common Antigens