IL‐15, which is trans‐presented by IL‐15Rα+ cells to neighboring IL‐2Rβ/γC+ cells, is crucial for the development of intestinal intraepithelial lymphocytes (IEL). Parenchymal cells have a major role in the trans‐presentation of IL‐15 to IELs; however, the specific identity of this cell type is unknown. Since trans‐presentation requires cell‐cell contact, we hypothesize that intestinal epithelial cells (IEC) are the parenchymal cell trans‐presenting IL‐15 to IELs. To determine whether IECs trans‐present IL‐15 to developing IELs, we developed a mouse model with IL‐15Rα expressed exclusively by the IECs. This model was generated by driving IL‐15Rα under the Villin promoter and crossing to the IL‐15Rα−/− background. Analysis of these transgenic mice detected high levels of IL‐15Rα by the IECs. Among the IELs, Thy1‐ CD8αα TCRαβ and TCRγδ subsets were restored to normal or higher levels as compared to control and IL‐15Rα−/− mice. The increases in cell number did not appear to be the result of cell expansion as no differences in proliferation rate was detected among transgenic, control, or IL‐15Rα−/− mice. Collectively, this study demonstrates that IL‐15Rα expression by IECs alone is completely sufficient to direct all the IL‐15‐mediated events driving the development of CD8αα IELs. This research is supported by NIH grant AI070910 and the MDACC Trust Fellowship.
Interleukin-15 (IL-15 IntroductionThe generation and maintenance of memory CD8 T cells is regulated by multiple mechanisms that involve both early programming of memory T-cell precursors as well as a continuous supply of external signals. 1,2 Whereas the events and signals that program memory precursors are not well understood, interleukin-15 (IL-15) has clearly been shown to drive the generation and maintenance of memory CD8 T cells. 3,4 The recent evidence that IL-15 is delivered through the mechanism of transpresentation via IL-15R␣ by cell-cell contact 5 opens up many questions in the field of memory CD8 T-cell homeostasis, the foremost being the identity of the cell transpresenting IL-15 to memory CD8 T cells.To better understand how IL-15 transpresentation is regulated, the identity of the cell type mediating IL-15 transpresentation must be known. Studies attempting to address this have found that either parenchymal or hematopoietic cells mediate transpresentation, depending on the responding lymphocyte. 6,7 This finding is seminal as it shows that cells can be in an IL-15R␣ ϩ environment and remain ignorant to IL-15. Considering that IL-15R␣ is ubiquitously expressed, it is surprising that the responding cell has such strict requirements for a specific cell to transpresent IL-15. 8 In contrast to IL-15R␣ expression, IL-15 protein is not believed to be expressed by many IL-15R␣-expressing cells (ie, T cells); however, expression of IL-15 has been difficult to determine as reagents detecting IL-15 protein have been limited. As such, multiple studies using functional readouts have found that coexpression of IL-15 and IL-15R␣ is integral for a cell to transpresent IL-15. [9][10][11] These observations emphasize that the identity of an IL-15 transpresenting cell may not simply be implied by the expression of IL-15R␣ but rather is better determined through functional analysis.For memory CD8 T cells, in vivo studies found that IL-15R␣-expressing hematopoietic cells are the dominant cell types driving homeostatic proliferation. 7,12 The hematopoietic cells providing the IL-15 signal are RAG-1-independent, indicating that IL-15 transpresentation is not mediated by either T or B lymphocytes. 9 As DCs, monocytes, and macrophages have been shown to express IL-15R␣ protein and are capable of inducing IL-15, 13,14 these cells are potential mediators of IL-15 transpresentation. Indeed, bone marrow (BM)-derived DCs and some monocytic cell lines can transpresent IL-15 in vitro 5 ; however, whether their analogous in vivo counterparts transpresent IL-15 to CD8 T cells is not known. Since IL-15 transpresentation requires cell-cell interactions and DCs have a natural propensity for T-cell interactions, DCs are a prime candidate to transpresent IL-15 to memory CD8 T cells. Therefore, the goal of this study was to examine the contribution of DCs in transpresentation of IL-15 to CD8 T cells.In this study, we demonstrate that DCs transpresent IL-15 to CD8 T cells driving specific functions during differentiation. Although IL-15 ...
Scleral fixation of IOLs using trocar cannulas or scleral tunnels is an effective surgical option for the treatment of aphakia or IOL dislocation. Both techniques result in significant visual improvement with minimal postoperative complications.
IntroductionBreast feeding has long term effects on the developing immune system which outlive passive immunization of the neonate. We have investigated the transfer of milk immune cells and examined the result of transfer once the recipients were adult.MethodsNon-transgenic mouse pups were foster-nursed by green fluorescent protein (GFP) transgenic dams for 3 weeks and the fate of GFP+ cells was followed by FACS analysis, immunohistochemistry and RT-PCR for GFP and appropriate immune cell markers. Pups suckled by non-transgenic dams served as controls.ResultsDespite a preponderance of B cells and macrophages in the stomach contents of the pups, most cells undergoing trans-epithelial migration derived from the 3–4% of milk cells positive for T lymphocyte markers. These cells homed to the spleen and thymus, with maximal accumulation at 3–4 weeks. By sensitizing dams with an antigen which elicits a T cell-mediated delayed-type-hypersensitivity (DTH) response, we determined that nursing by a sensitized dam (compared to a non-sensitized dam) amplified a subsequent DTH response in females and yet suppressed one in males.DiscussionThese results suggest that clinical evaluation weighing the pros and cons of nursing male versus female children by mothers with genetically-linked hypersensitivity diseases, such as celiac disease and eczema, or those in regions of the world with endemic DTH-eliciting diseases, such as tuberculosis, may be warranted.
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