The Translational Relevance of Human Circulating Memory Cutaneous Lymphocyte-Associated Antigen Positive T Cells in Inflammatory Skin Disorders

Abstract

Circulating memory T cells are heterogeneous in their tissue tropism. The skin-seeking T cell subset expresses the cutaneous lymphocyte-associated antigen (CLA) on their surface. CLA+ memory T cells not only migrate from blood to skin but also recirculate between blood and skin. Studying CLA+ memory T cells in cutaneous diseases has allowed a better understanding of immune-inflammatory mechanisms that take place. The analysis of the phenotypical features of these cells, their antigen specificity, cytokine production profile, and changes in relationship to clinical status and therapies among other characteristics have led to the concept that they constitute peripheral cellular biomarkers in T cell-mediated cutaneous conditions. CLA+ memory T cells are of relevance in the pathogenesis of several cutaneous diseases, such as psoriasis (PSO), atopic dermatitis, vitiligo, and drug-induced allergic reactions, to name a few. The interaction of circulating CLA+ T cells with skin-resident cells has been investigated in different ex vivo coculture models made out of clinical samples. Interestingly, microbes that are present in the skin or related with human skin diseases are preferentially recognized by CLA+ T cells. Thus, the interaction of Streptococcus pyogenes with CLA+ T cells in PSO is providing novel concepts that help to understand disease immunopathogenesis. The goal of this review is to present latest results in the field of CLA+ T cells in T cell-mediated inflammatory skin diseases and their translational relevance for human immunodermatology.

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“…This process is also accompanied by the change of phenotype of the naïve T cells, from CD45RA that are oen expressed as cutaneous lymphocyte-associated antigens (CLA) on their surface (known as CD45RA + CLA À ), to the effector memory T cells, CD45RO + CLA À . 70,[72][73][74] (3) The memory CD45RO + CLA À T cells are accompanied by the T h 1 and T h 17 cells to be carried out through the blood vessels from the dermis to the epidermis as the result of the intradermal proliferation of T-cells. 74 (4) In the epidermis, the natural killer T cells are responsible for direct antigen presentation due to their proximity to the keratinocytes.…”

“…This process is also accompanied by the change of phenotype of the naïve T cells, from CD45RA that are often expressed as cutaneous lymphocyte-associated antigens (CLA) on their surface (known as CD45RA + CLA − ), to the effector memory T cells, CD45RO + CLA − . 70,72–74…”

CLA + memory T cells in atopic dermatitis

“…45 Based on the skin tropism, recirculation, and specific responses of CLA + T cells, it may be considered that this population, constitutes the subset of CD45RO + population that is closer to SALT features and may be contemplated representative of the skin-associated adaptive immune system (Table I). 46 Since the discovery of the CLA antigen numerous human studies have confirmed the implication of circulating CLA + , but not CLA -, memory T cells in diverse T cell-mediated cutaneous diseases with various pathological mechanisms. Circulating CLA + T cells respond to antigens, allergens, viruses, bacterial superantigens and drugs, with the common feature of being involved in the physiopathological mechanisms of distinct skin diseases such as dengue, leprosy, drug-induced allergic reactions, or alopecia areata, to name a few (Table I).…”

“…Additionally, their phenotype in circulation has been reported to correlate with the clinical activity and response to treatment of cutaneous diseases. 46…”

Human CLA+ Memory T Cell and Cytokines in Psoriasis

“…Indeed, the fact that CLA + memory T cells recirculate between skin and blood was evidenced by action of efalizumab (a monoclonal antibody targeting the CD11a subunit of LFA-1 molecule that blocked lymphocyte extravasation toward the skin) in psoriasis (11) and atopic dermatitis (12) patients, which proved clinical improvement but also resulted in a lymphocytosis effect of CLA + T cells that caused relapses after treatment discontinuation (13). The recirculating capacity of CLA + memory T cells is key to their value in translational research, due to their ability to reflect the immune abnormalities found in numerous human cutaneous conditions such as psoriasis, atopic dermatitis, contact dermatitis, drug-induced allergic reactions, vitiligo, herpes simplex, rosacea, cutaneous T cell lymphoma, or alopecia areata (14,15).…”