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Recent investigations have indicated a role for antigen-specific T lymphocytes in the local skin immunity. The cutaneous lymphocyte antigen (CLA) is supposed to represent a skin-homing receptor for T cells. Inhibition experiments with specific monoclonal antibody demonstrate that CLA participates in selective transendothelial migration of memory/effector T cells in vitro by interaction with E-selectin on endothelial cell layers after activation with proinflammatory cytokines. In addition, the receptor-ligand pairs VLA-4/VCAM-1 and LFA-1/ICAM-1 are involved in this process. Moreover, only CLA+, CD45RO+ (memory/effector) T cells freshly isolated from peripheral blood of patients with allergic contact dermatitis or atopic dermatitis specifically proliferate in response to the respective allergen. CLA-, CD45RO- T cells from these patients do not respond to the allergens. In contrast, memory T cells from asthmatic individuals and patients with both asthma and atopic dermatitis express the allergen specificity in both T cell subsets. Tetanus toxoid, a systemically acting antigen, also induces a proliferative response in both CLA+ and CLA- memory/effector T cell subsets. These results strongly support the selective role of CLA in homing T cells to the cutaneous tissues and therefore playing a role in the local immunity and inflammatory reactions of the skin.

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.