Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients

Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Science translational medicine (Impact Factor: 15.84). 01/2012; 4(117):117ra7. DOI: 10.1126/scitranslmed.3003008
Source: PubMed


Cutaneous T cell lymphoma (CTCL) is a cancer of skin-homing T cells with variants that include leukemic CTCL (L-CTCL), a malignancy of central memory T cells (T(CM)), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (T(EM)). We report that low-dose alemtuzumab (αCD52) effectively treated patients with refractory L-CTCL but not MF. Alemtuzumab depleted all T cells in blood and depleted both benign and malignant T(CM) from skin, but a diverse population of skin resident T(EM) remained in skin after therapy. T cell depletion with alemtuzumab required the presence of neutrophils, a cell type frequent in blood but rare in normal skin. These data suggest that T(CM) were depleted because they recirculate between the blood and the skin, whereas skin resident T(EM) were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of interleukin-4 and higher amounts of interferon-γ. Moreover, there was a marked lack of infections in alemtuzumab-treated L-CTCL patients despite the complete absence of T cells in the blood, suggesting that skin resident T(EM) can protect the skin from pathogens even in the absence of T cell recruitment from the circulation. Together, these data suggest that alemtuzumab may treat refractory L-CTCL without severely compromising the immune response to infection by depleting circulating T(CM) but sparing the skin resident T(EM) that provide local immune protection of the skin.

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    • "T RM cells have been identified at barrier surfaces in mice and non-human primates (Bevan, 2011; Sheridan and Lefrancois, 2011; Masopust and Picker, 2012), with similar cells characterized in human skin (Clark et al., 2012) and this pool is of interest as a critical first line of defense against infection. While there are numerous questions about the pathways involved in establishment and maintenance of T RM , the pool found in the mouse small intestine IEL pool is especially well-characterized. "
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