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This Top Read demonstrates a newly discovered DAP12-dependent mechanism of T cell recruitment to sites of inflammation. Prior to the work of Shao et al. (p. 37), it was unknown whether selectin signaling could activate integrins in effector T cells. The authors showed that the slow rolling of Th1 cells on both P- and E-selectins was mediated through an ICAM-1 and integrin αLβ2 interaction. In neutrophils, it has been shown that, selectin activation led to phosphorylation of ITAM proteins. Expression of DAP12, an ITAM-containing protein, in Th1 cells, was required for selectin-initiated signaling and activation of integrin αLβ2. DAP12-deficient Th1 cells adhered normally but spread less effectively than wildtype cells, indicating that DAP12 is required for signaling cascades that strengthen adhesion. This was corroborated by in vivo results demonstrating reduced homing of DAP12-deficient Th1 cells to inflamed tissue. Together, these data provide new insights on the migration mechanisms of effector T cells.

Unlike lymph nodes and mucosal lymphoid tissue, in which the movement of leukocytes is well defined, the lymphocyte turnover mechanisms and kinetics in intra-abdominal fat-associated lymphoid tissues have only been partially explored. In this Top Read, Jia et al. (p. 23) identified and characterized serous lymphoid tissues that can efficiently bind B lymphoma cells and normal B lymphocytes. These tissues, denoted as foliate lymphoid aggregates (FLAgs), owing to the leaf-like appearance, were connected to the omental and mesenteric adipose tissue or peritoneal membrane via a stalk. FLAgs had a partially differentiated stromal architecture and displayed partial compartmentalization of T/B cells based on their chemokine receptor pattern. Despite a lack of lymphatic vessels, lymphocytes within FLAgs gained access to the mesenteric lymph nodes via capillaries. In addition, FLAgs were destination sites for blood-borne leukocytes via peripheral lymph node addressin–positive high endothelial venules, and a partial utilization of l-selectin for homing. In summary, this study demonstrates that serous lymphoid aggregates function as peritoneal collection sites for both normal B cells and lymphoma cells. Additional work is needed to further elucidate factors facilitating movement of lymphocytes within mesenteric lymphatic capillaries.

This Top Read shows that patrolling monocytes are necessary for antitumor NK cell recruitment, activation, and cytotoxicity. To study the impact of patrolling monocytes on NK cell function, Narasimhan et al. (p. 192) used a mouse model (E2^−/−) wherein nonclassical patrolling monocytes were specifically depleted. Compared with wild-type (WT) mice, tumor-bearing E2^−/− animals showed a significant increase in metastatic tumor burden, including overall tumor volume and lung metastases. These changes correlated with a decreased frequency of both total and activated NK cells, indicating that the lack of patrolling monocytes may impact NK cell antitumor immunity. Indeed, the absence of patrolling monocytes was associated with increased expression of inhibitory receptors, NKG2A and CD94, on NK cells following metastasis. Additionally, the fraction of educated NK cells expressing the stimulatory receptor Ly49D was significantly decreased in E2^−/− mice bearing metastatic tumors when compared with WT mice. Finally, the authors noted a 30% reduction in degranulation of NK cells in the absence of patrolling monocytes. Together, these data demonstrate the importance of nonclassical, patrolling monocytes in the generation of an effective NK cell antitumor response.

Infection with CMV continually drives the production of highly differentiated virus-specific CD8⁺ T cells in an Ag-dependent manner, a phenomenon known as memory inflation. Interestingly, memory inflation is confounded by a process of competition for access to limited amounts of the cognate Ag, in which success leads to preferential expansion of the fittest clones. In this Top Read, Smith et al. (p. 112) explored the clonal dynamics of memory inflation by tracking mixtures of two congenically marked OT-I cell populations in mice infected with murine CMV (MCMV) expressing OVA. Irrespective of numerical dominance, stochastic expansions were observed such that dominant and subdominant OT-I cell populations were maintained at stable frequencies over time. Examination of endogenous CD8⁺ T cell populations for two classic inflation-associated epitopes, M38 and IE3, demonstrated that multiple clonotypes underwent Ag-driven proliferation during latent infection with MCMV. Furthermore, the corresponding CD8⁺ T cell repertoires were stable over time and dominated by a persistent clonotype. Collectively, these data demonstrate that clonal expansions occur in a sporadic manner but are substantial enough to maintain an oligoclonal pool of inflationary CD8⁺ T cells during chronic MCMV infection.