CXCR6 promotes dermal CD8+ T cell survival and transition to long-term tissue residence.

Tissue resident memory T cells (TRM) provide protection against local re-infection, and yet the interstitial signals that govern their formation and persistence remain poorly defined. Here, we show that antigen-dependent induction of the chemokine receptor CXCR6, is a conserved adaptation to peripheral tissue infiltration that promotes TRM formation after viral infection. Deficient TRM formation in the absence of CXCR6 was not explained by trafficking as CXCR6 was not required for tissue entry, was dispensable for the early accumulation of antigen-specific CD8+ T cells in skin, and did not restrain their exit.

T lymphocyte-specific deletion of SHP1 and SHP2 promotes activation-induced cell death of CD4 T cells and impairs antitumor response.

SHP1 (PTPN6) and SHP2 (PTPN11) are closely related protein-tyrosine phosphatases (PTPs), which are autoinhibited until their SH2 domains bind paired tyrosine-phosphorylated immunoreceptor tyrosine-based inhibitory/switch motifs (ITIMs/ITSMs). These PTPs bind overlapping sets of ITIM/ITSM-bearing proteins, suggesting that they might have some redundant functions. By studying T cell-specific single and double knockout mice, we found that SHP1 and SHP2 redundantly restrain naïve T cell differentiation to effector and central memory phenotypes, with SHP1 playing the dominant role.

T Lymphocyte-Specific Deletion of SHP1 and SHP2 Promotes Activation-Induced Cell Death of CD4+ T Cells and Impairs Antitumor Response.

Unlabelled: SHP1 (PTPN6) and SHP2 (PTPN11) are closely related protein-tyrosine phosphatases (PTPs), which are autoinhibited until their SH2 domains bind paired tyrosine-phosphorylated immunoreceptor tyrosine-based inhibitory/switch motifs (ITIMs/ITSMs). These PTPs bind overlapping sets of ITIM/ITSM-bearing proteins, suggesting that they might have some redundant functions. By studying T cell-specific single and double knockout mice, we found that SHP1 and SHP2 redundantly restrain naïve T cell differentiation to effector and central memory phenotypes, with SHP1 playing the dominant role.

Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes.

Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (T) play an important role in site-specific immune memory, yet how LN T form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8 T cells as they seeded skin and LN T using a model of vaccinia virus-induced skin infection.

Lymphatic vessel transit seeds precursors to cytotoxic resident memory T cells in skin draining lymph nodes.

Resident memory T cells (T) provide rapid, localized protection in peripheral tissues to pathogens and cancer. While T are also found in lymph nodes (LN), how they develop during primary infection and their functional significance remains largely unknown. Here, we track the anatomical distribution of anti-viral CD8 T cells as they simultaneously seed skin and LN T using a model of skin infection with restricted antigen distribution.

CXCR6 promotes dermal CD8 T cell survival and transition to long-term tissue residence.

Unlabelled: Tissue resident memory T cells (T ) provide protection against local re-infection, and yet the interstitial signals necessary for their formation and persistence remain incompletely understood. Here we show that antigen-dependent induction of the chemokine receptor, CXCR6, is a conserved adaptation to peripheral tissue infiltration that promotes T formation after viral infection. Deficient T formation in the absence of CXCR6 was not explained by canonical trafficking as CXCR6 was not required for tissue entry, was dispensable for the early accumulation of antigen-specific CD8 T cells in skin, and did not restrain their exit.

Infection-induced lymphatic zippering restricts fluid transport and viral dissemination from skin.

Lymphatic vessels are often considered passive conduits that flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests that lymphatic vessels actively regulate diverse processes from antigen transport to leukocyte trafficking and dietary lipid absorption. Here we tested the hypothesis that infection-induced changes in lymphatic transport actively contribute to innate host defense.

Tumor-draining lymph nodes: At the crossroads of metastasis and immunity.

Early engagement of the lymphatic system by solid tumors in peripheral, nonlymphoid tissues is a clinical hallmark of cancer and often forecasts poor prognosis. The significance of lymph node metastasis for distant spread, however, has been questioned by large-scale lymph node dissection trials and the likely prevalence of direct hematogenous metastasis. Still, an emerging appreciation for the immunological role of the tumor-draining lymph node has renewed interest in its basic biology, role in metastatic progression, antitumor immunity, and patient outcomes.