Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen.
The cutaneous lymphocyte-associated antigen (CLA) is the major T cell ligand for the vascular adhesion molecule E-selectin, and it has been proposed to be involved in the selective targeting of memory T cells reactive with skin-associated Ag to cutaneous inflammatory sites. To further investigate the relation of CLA and cutaneous T cell responses, we analyzed the CLA phenotype of circulating memory T cells in patients with allergic contact dermatitis and atopic dermatitis (AD) alone vs in patients manifesting bronchopulmonary atopy (asthma with or without AD) and nonallergic individuals. Significant T cell proliferative responses to Ni, a contact allergen, and to the house dust mite (HDM), an allergen to which sensitization is often observed in AD and/or asthma, was noted only in allergic and atopic individuals, respectively. When the minor circulating CLA+CD3+CD45RO+ subset was separated from the major CLA-CD3+CD45RO+ subpopulation in Ni-sensitive subjects, the Ni-dependent memory T cell response was largely confined to the CLA+ subset. A similar restriction of the T cell proliferative response to the CLA+ memory subset was observed for HDM in patients with AD alone. In HDM-sensitive patients with asthma with or without AD, however, the CLA- subset exhibited a strong antigen-dependent proliferation, in contrast to patients with AD alone, whose CLA- subset proliferated very weakly to HDM. In asthma with or without AD, the HDM-dependent proliferation slightly predominated in the CLA- when compared to the CLA+ subset. The functional linkage between CLA expression and disease-associated T cell effector function in AD was also demonstrated by the finding that the circulating CLA+ T cell subset in AD patients, but not nonatopic controls, selectively showed both evidence of prior activation (human histocompatibility antigen-DR expression) and spontaneous production of interleukin 4 but not interferon-gamma. Taken together, these observations demonstrate the correlation of CLA expression on circulating memory T cells and disease-associated memory T cell responses in cutaneous hypersensitivity, and they suggest the existence of mechanisms capable of sorting particular T cell Ag specificities and lymphokine patterns into homing receptor-defined memory subsets.
Santamaria Babi
L F
LF
Swiss Institute of Allergy and Asthma Research, Davos.
Picker
L J
LJ
Perez Soler
M T
MT
Drzimalla
K
K
Flohr
P
P
Blaser
K
K
Hauser
C
C
D000328:Adult; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis*; D008925:Mites / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000032:analysis*; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing