Neutrophils Transport Antigen from the Dermis to the Bone Marrow, Initiating a Source of Memory CD8+ T Cells

Duffy, D. , et al. Immunity 37, 917-929. (2012).

Speaker: Alan Hsu (許翊輝)                                          Time: 13:00~14:00, April 10, 2013

Commentator: Dr. Shun-hua Chen (陳舜華 老師)      Place: Room 601

Abstract

        The bone marrow is a well-studied and long known organ of hematopoietic properties, yet its role as a secondary immune organ is only recently being studied and researched. The BM was shown in previous studies to be a preferential organ for CD8 T cell priming and in some cases CD4 T cells as well. The authors showed in their previous studies that, when mice was injected with Modified Vaccinia Ankara (MVA) virus intradermally (i.d.), neutrophils were one of the first cells to arrive at the dermal infection site, and then mediate the transport of MVA virus to the draining lymph nodes (dLN). Another study showed that senescent neutrophils sometimes migrate to the BM to be engulfed by BM resident phagocytes. Taken together the authors set out to test the hypothesis; of which during i.d. infection by MVA virus, neutrophils would carry the virus from the dermis to the bone marrow priming the cells there thus causing a T cell immune response. They found that CD8 T cell levels rose on day 4 P.I. and this phenomenon was still seen when dLN cell migration was inhibited, but the BM T cell priming effect was lost in cases of neutrophil depletion or in Ccr1^-/-mice. To solidify the concept, neutrophils were cultured with MVA-GFP and then injected into mice, where they saw these specific neutrophils in the BM at 4h P.I. . Furthermore, depletion of CD11b⁺F4/80⁺ myeloid APC cells in the BM will hinder the T cell priming response, whereas T cell levels in the LNs had no effect, stating that those cells were necessary for T cell priming in the BM. While comparing the phenotype between BM and dLN primed T cells, they found that BM primed T cells expressed higher levels of proliferation cytokine receptors IL-7R, IL-15R, and IL-2R while also higher amounts of CD44 an activation marker. Gene expression profiles also differed between the two, while Cell death and inflammation genes were lower but immune cell trafficking and cell growth and proliferation genes were higher in BM primed T cells compared with dLN primed T cells. All in all they provided evidence on how an antigen is transported to the BM, and elicit a specific CD8 T cell immune response different from what we see in the LN.

References:

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2.       Tokoyoda, K., Hauser, A.E., Nakayama, T., and Radbruch, A. (2010). Organization of immunological memory by bone marrow stroma. Nature reviews. Immunology 10, 193-200.