CD57 expression on CD8+ T cells determines lack of proliferation ability, associated with short telomeres, defining replicative senescence that occurs in conditions of chronic immune activation, such as HIV-1 infection 
. CD57+CD8+ T cells exhibit up-regulated expression of cytotoxicity genes, such as perforin, granulolysin, and granzyme B, indicating increased cytotoxic ability, and a higher IFN-gamma and TNF-alpha production upon TCR stimulation 
. On CD4+ T cells, CD57 expression has also been associated with decreased proliferation capacity, and affects CD4+ T cell function, being associated with higher IFN-gamma but lower IL-2 production 
. Whether CD57+CD4+ and CD57+CD8+ T cells can contribute to psoriasis immunopathogenesis remains poorly understood. One previous study has demonstrated by immunohistochemistry the presence of CD57+ cells in psoriasis patients, showing higher numbers in involved epidermis and papillary dermis compared to uninvolved skin, while in reticular dermis, uninvolved skin exhibited higher numbers of CD57+ cells compared to normal control skin 
CD57+CD8+ T cells exhibit a phenotype compatible with increased ability to migrate to tissues without further cycling 
. They express higher levels of CX3CR1 than CD57−CD8+ T cells, which can dictate their migration to tissues 
. Interestingly, 2 polymorphisms in the CX3CR1 gene were found to be associated with psoriasis 
. One of these was a coding polymorphism with higher frequency in healthy controls compared to cases that is thought to impair the ability of CX3CR1 to adhere to its ligand CX3CL1 
. These genetic data support the notion that recruitment of CD57+ lymphocytes into the skin via the CX3CR1-CX3CL1 axis may be important in the pathogenesis of psoriasis.
In this study, we found higher CD57 expression on CD4+ and CD8+ T cells in unaffected skin of psoriasis patients compared to lesional skin. In recent years, much attention has been given to non-lesional unaffected skin of psoriasis patients, where quiescent auto-reactive T cells named skin-resident T cells have been demonstrated 
. CD57 is a marker of chronic antigenic stimulation. We could hypothesize that some of the quiescent T cells present in non-lesional sites express CD57 as a result of previous antigenic stimulation. We do not know whether the site of unaffected skin biopsy has previously been a lesional site. The persistence of a population of CD8+ T cells in the dermis of resolved psoriasis lesions after treatment has been demonstrated, and points to the possibility of lesional memory 
. Alternatively, as CD57 expression on T cells is associated with a decreased replicative capacity, the high cellular turnover at lesional sites could result in the lower survival of CD57+ T cells, leading to the finding of lower CD57 expression in psoriasis lesions.
Unlike atopic dermatitis, where clear differences have been shown between unaffected skin and normal skin from healthy controls, in psoriasis unaffected skin has been considered largely similar to normal skin 
. However, differences in gene expression between uninvolved psoriasis skin and normal control skin have also been shown 
. We have found higher CD57 expression in unaffected psoriasis skin compared to lesional skin. CD57 expression on T cells has not been described in normal control skin. We believe that the finding of higher CD57 expression is specific to uninvolved psoriasis skin, and is not a consequence of similarities between uninvolved psoriasis skin and normal control skin.
Th-17 cells constitute a subset of CD4+ T cells that have the distinct characteristics of being stimulated by IL-23, and producing IL-17A 
. IL-17A has been implicated as an important cytokine in the pathogenesis of psoriasis. IL-17 mRNA levels are higher in lesional skin in psoriasis than in normal skin from healthy controls 
. The presence of IL-17A in lesional tissue leads to the release of multiple inflammatory cytokines by keratinocytes, including TNF-alpha, IL-1, and IL-6 
. IL-17A can also induce angiogenesis and the production of antibacterial peptides 
. In addition, IL-17A induces keratinocyte expression of chemokine genes that lead to neutrophil migration, thus contributing to overall inflammation 
. That is in contrast with the effects of IFN-gamma, which induces preferential expression of CXCL9, CXCL10, and CXCL11, that bind to activated T cells containing CXCR3 
IL-22, another important cytokine for psoriasis pathogenesis, can be produced by CD4+ T and CD8+ T cells 
. IL-22 induces multiple anti-apoptotic and proliferative pathways through the Stat3 cascade and has the capacity of inducing keratinocyte proliferation through the down-regulation of keratinocyte differentiation genes, such as keratin 1 and fillagrin 
. IL-22 induces anti-microbial proteins such as beta-defensins and IL-22 mRNA expression is increased in psoriasis lesions compared to normal skin 
In this study, we were able to compare the relative production of IL-17 and IL-22, as well as IFN-gamma, IL-2, TNF-alpha, and IL-27, in lesional and unaffected skin on the same individuals. We found that CD4+ and CD8+ T cells isolated from lesional skin have a higher ability to produce IL-17A than their counterparts isolated from unaffected skin. We could hypothesize that T cells in lesional skin have acquired the ability to secrete this cytokine due to the local inflammatory environment or locally expressed antigens. IL-22 production by CD4+ T cells isolated from lesional skin was also higher than unaffected skin. They could correspond to Th-17 cells or Th-22 cells. We could also demonstrate IL-22 production by sorted CD8+ T cells from lesional skin in low amounts, in higher levels than unaffected skin. Interestingly, IL-22 production by CD4+ T cells isolated from lesional skin correlated with TNF-alpha, IFN-gamma, and IL-2. CD8+ T cells isolated from lesional skin exhibited a mixed cytokine profile between Th-17 and Th-1, as higher production of IFN-gamma, TNF-alpha, and IL-2 was also observed in lesional skin.
In conclusion, we were able to assess phenotypic characteristics and cytokine production by CD4+ and CD8+ T cells from lesional and unaffected skin from the same patients. We demonstrated that there are phenotypic and functional differences in T cells in different sites in the same individuals. Further studies are needed to elucidate the importance of unaffected tissue in psoriasis.