Targeted Delivery of Antigen to Activated CD169+ Macrophages Induces Bias for Expansion of CD8+ T Cells

Abstract

Macrophages expressing the sialic acidbinding lectin CD169 are involved in mounting antigen-specific T cell responses. Here, Edgar et al. describe a CD169-targeted liposome-based platform able to selectively activate and deliver antigen to these macrophages. This modular platform enabled control over antigen-specific CD4 + :CD8 + T cell ratios in vivo.

Antigen Cross-Presentation by Macrophages

“…Moreover, the specific antigen transfer seems to depend on the sialoadhesin CD169, which is involved in cell adhesion, because the use of Sn-KI mice, which expresses a mutated form of CD169, resulted in a reduced amount of antigen-positive CD8 + DCs (fluorescent ovalbumin) and a reduced amount of ovalbumin-specific IFN-γ-producing CD8 + lymphocytes ( 29 ). The immune stimulus of CD169 + macrophages is also important, because in vivo administration of liposomes targeted to CD169L, present on CD169 + macrophages, and containing ovalbumin and a TLR7 agonist induced expression of the activation markers CD86 and CD80 in the CD169 + macrophages and induced in vivo OT-I CD8 + T lymphocyte activation measured by proliferation, whereas only OT-II CD4 + T-cell responses were observed in absence of the TLR7 agonist ( 30 ). Altogether, it seems that murine CD169 + macrophages in the spleen contribute to cross-presentation either directly or by transferring antigens to CD8 + DCs in the spleen.…”

HIV-Captured DCs Regulate T Cell Migration and Cell-Cell Contact Dynamics to Enhance Viral Spread

“…Retained HIV particles can then access target CD4+ T cells through DC:T cell interactions in a way that is analogous to the capture of ganglioside-rich exosomes by mDCs and amplification of the immune response without antigen reprocessing ( Izquierdo-Useros et al., 2014 ; Nasr et al., 2014 ). Subcapsular sinus (SCS) macrophages also express Siglec-1 (CD169) ( Asano et al., 2011 ; Edgar et al., 2019 ; Grabowska et al., 2018 ; Hammonds et al., 2017 ; Junt et al., 2007 ; Saunderson et al., 2014 ; Uchil et al., 2018 ) that play a vital role in pathogen capture and transport to DCs or the B cell follicles ( Grabowska et al., 2018 ; Phan et al., 2009 ; Veninga et al., 2015 ). HIV and MLV (murine leukemia virus) have been shown to exploit SCS macrophages to access target CD4 T cells and B cells, respectively, and facilitate efficient viral spread in vivo ( Sewald et al., 2015 ).…”

Nanomedicine-mediated alteration of the pharmacokinetic profile of small molecule cancer immunotherapeutics

“…Reprinted with permission from Elsevier sites [39]. Furthermore, phospholipid 1V270 has been extensively incorporated in liposomes as a vaccine adjuvant [110,111].…”

“…After systemic administration of the phospholipid 1V270, the strongest immune activation was observed for DCs in the tumor and draining lymph nodes, resulting in a tumor-specific systemic immune response capable of eliminating tumor cells at distal sites [ 39 ]. Furthermore, phospholipid 1V270 has been extensively incorporated in liposomes as a vaccine adjuvant [ 110 , 111 ].

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