MAIT cells are imprinted by the microbiota in early life and promote tissue repair.

How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)-producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.

Primary Cutaneous T-Cell Lymphomas Showing Gamma-Delta (γδ) Phenotype and Predominantly Epidermotropic Pattern are Clinicopathologically Distinct From Classic Primary Cutaneous γδ T-Cell Lymphomas.

Primary cutaneous gamma-delta (γδ) T-cell lymphoma is a rare disease that typically involves the dermis and subcutis. Cases of primary cutaneous T-cell lymphomas showing γδ phenotype and predominantly epidermotropic pattern (EγδTCL) are not well defined. In this series, cases of primary cutaneous T-cell lymphomas showing γδ phenotype were reviewed and classified as predominantly epidermotropic (EγδTCL) when >75% of lymphoma cells resided in the epidermis or predominantly dermal and/or subcutaneous (DSγδTCL). Clinical, pathologic, and immunophenotypic features were compared in 27 biopsies from 13 patients of EγδTCL and 13 biopsies from 7 patients of DSγδTCL. The lymphoma cells were diffusely positive for CD3 and T-cell receptor (TCR)γ, mostly positive for granzyme B and TIA-1, variably positive for CD8, CD7, and CD30, and negative for CD4 and TCRß. Two patients with EγδTCL had dissemination to lymph nodes and 1 to the lung; 1 patient with DSγδTCL had gastrointestinal involvement. The median survival of patients with EγδTCL was not reached, and with a median follow-up of 19.2 months, 3/13 died. In contrast, the median survival of patients with DSγδTCL was 10 months, and after a median follow-up of 15.6 months, 5/5 died (P<0.01). EγδTCL is a rare presentation of cutaneous T-cell lymphoma that can be distinguished from DSγδTCL based on the extent of epidermotropism and has a better prognosis and longer median survival than DSγδTCL. However, although EγδTCL resembles mycosis fungoides clinically and histologically, a subset of EγδTCL is more likely to behave more aggressively than typical mycosis fungoides.

Primary Cutaneous Gamma-Delta (γ/δ) T-cell Lymphoma: An Unusual Case With Very Subtle Histopathological Findings.

Primary cutaneous γ/δ T-cell lymphoma (PCGDTCL) accounts for <1% of all primary cutaneous lymphomas. These rare diseases are believed to originate from γ/δ lymphocytes. Clinical presentation may vary, but its clinical behavior is regarded as aggressive and long-term survival is anecdotal. This study describes the case of a 60-year-old man with multiple, rapidly progressing skin plaques on his head, arms, torso, buttocks, and legs. The histopathological changes seen in the skin biopsy were extraordinarily subtle with mild epidermal hyperplasia and a very sparse lymphoid infiltrate involving epidermis and superficial dermis. Immunohistochemical studies revealed the atypical intraepidermal hyperchromatic cells to be mostly positive for CD3 and CD7 and negative for both CD4 and CD8. The intraepidermal atypical lymphocytes were positive for TCR gamma, and negative for betaF1 and CD56. The clinical, morphologic, and immunohistochemical findings supported the diagnosis of PCGDTCL. This case illustrates a case of epidermotropic variant of PCGDTCL that, albeit a bland histopathological presentation, was associated with an aggressive clinical behavior.