Induction of vaginal-resident HIV-specific CD8 T cells with mucosal prime–boost immunization

Tan, Hyon-Xhi; Wheatley, Adam K.; Esterbauer, Robyn; Jegaskanda, Sinthujan; Glass, Joshua Julian; Masopust, David; Rose, Robert De; Kent, Stephen J.

doi:10.1038/mi.2017.89

Cited by 41 publications

(43 citation statements)

References 67 publications

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“…92 The activation of HIV-specific CD8 + T RM cells results in the recruitment of both adaptive and innate immune cells in the VM. 88 On the other hand, T RM cells can lyse infected target cells directly (Fig. 1).…”

Section: Cd8 + T Rm Cells In Anti-viral Immunitymentioning

confidence: 99%

“…25 In the respiratory tract, T RM cells may confer protective immunity against viruses such as RSV, 80,85 Sendai virus, 86 and influenza. 36,73,87,88 High levels of lung-resident T RM cells are induced by administration of the mucosal Sendai virusengineered recombinant anti-TB vaccine (SeV85AB), which leads to a rapid and strong recall response against Mtb challenge infection. 89 Generation of T RM cells by intranasal vaccination of RSV antigen-expressing MCMV results in earlier T cell responses and viral clearance after RSV challenge.…”

Section: Cd8 + T Rm Cells In Anti-viral Immunitymentioning

confidence: 99%

“…91 HIV-specific T RM cells are established in the VM and are capable of initiating a tissue-wide immune response after combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. 88 Upon activation of T RM cells, they can rapidly secrete a number of proinflammatory cytokines, such as IFN-γ, TNF-α and IL-12 ( Fig. 1).…”

Section: Cd8 + T Rm Cells In Anti-viral Immunitymentioning

confidence: 99%

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Tissue-resident lymphocytes: from adaptive to innate immunity

et al. 2019

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Efficient immune responses against invading pathogens often involve coordination between cells from both the innate and adaptive immune systems. For multiple decades, it has been believed that CD8 + memory T cells and natural killer (NK) cells constantly and uniformly recirculate. Only recently was the existence of noncirculating memory T and NK cells that remain resident in the peripheral tissues, termed tissue-resident memory T (T RM) cells and tissue-resident NK (trNK) cells, observed in various organs owing to improved techniques. T RM cells populate a wide range of peripheral organs, including the skin, sensory ganglia, gut, lungs, brain, salivary glands, female reproductive tract, and others. Recent findings have demonstrated the existence of T RM in the secondary lymphoid organs (SLOs) as well, leading to revision of the classic theory that they exist only in peripheral organs. trNK cells have been identified in the uterus, skin, kidney, adipose tissue, and salivary glands. These tissue-resident lymphocytes do not recirculate in the blood or lymphatic system and often adopt a unique phenotype that is distinct from those of circulating immune cells. In this review, we will discuss the recent findings on the tissue residency of both innate and adaptive lymphocytes, with a particular focus on CD8 + memory T cells, and describe some advances regarding unconventional T cells (invariant NKT cells, mucosal-associated invariant T cells (MAIT), and γδ T cells) and the emerging family of trNK cells. Specifically, we will focus on the phenotypes and functions of these subsets and discuss their implications in anti-viral and anti-tumor immunity.

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Section: Cd8 + T Rm Cells In Anti-viral Immunitymentioning

confidence: 99%

Section: Cd8 + T Rm Cells In Anti-viral Immunitymentioning

confidence: 99%

Section: Cd8 + T Rm Cells In Anti-viral Immunitymentioning

confidence: 99%

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Tissue-resident lymphocytes: from adaptive to innate immunity

et al. 2019

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“…This is done, for instance, by topical delivery of vaccine vectors, which results in T cell activation by dendritic cells in lymphoid tissues draining the site of application, followed by T cell migration to the mildly inflamed target tissue and subsequent formation of CD8 + CD103 + T RM cells. Examples such approaches include cervico‐vaginal immunization with papilloma virus vectors encoding model antigens, such as M/M2 from respiratory syncytial virus (RSV) or glycoproteins B and D from HSV, as well as combined intranasal and intravaginal immunization with IAV vectors expressing HIV p24 . Protective T RM cells in genital mucosa have also been generated by combined topical application of inactivated Chlamydia trachomatis elementary bodies with charge‐switched synthetic adjuvant particles .…”

Section: Trm Cells Orchestrate Immediate Local Immunitymentioning

confidence: 99%

Tissue‐resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance

Gebhardt

Palendira

Tscharke

et al. 2018

Immunological Reviews

153

146

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A large proportion of memory T cells disseminated throughout the body are non-recirculating cells whose maintenance and function is regulated by tissue-specific environmental cues. These sessile cells are referred to as tissue-resident memory T (T ) cells and similar populations of non-recirculating cells also exist among unconventional T cells and innate lymphocyte cells. The pool of T cells is highly diverse with respect to anatomical positioning, phenotype, molecular regulation and effector function. Nevertheless, certain transcriptional programs are shared and appear as important unifying features for the overall population of T cells and tissue-resident lymphocytes. It is now widely appreciated that T cells are a critical component of our immune defense by acting as peripheral sentinels capable of rapidly mobilizing protective tissue immunity upon pathogen recognition. This function is of particular importance in anatomical sites that are not effectively surveilled by blood-borne memory T cells in absence of inflammation, such as neuronal tissues or epithelial compartments in skin and mucosae. Focusing on the well-characterized subtype of CD8 CD69 CD103 T cells, we will review current concepts on the generation, persistence and function of T cells and will summarize commonly used tools to study these cells. Furthermore, we will discuss accumulating data that emphasize localized T responses as an important determinant of tissue homeostasis and immune defense in the context of microbiota-immune interactions, persistent infections and cancer surveillance.

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“…[165] In a mouse study, they demonstrated that immunization with recombinant influenza-HIV vectors via combination intranasal and intravaginal administration resulted in localization of HIV-specific tissue-resident memory CD8 T cells in the vaginal mucosa. [166] Another study involving rhesus macaques, published in 2018, showed that combination adenovirus and protein vaccines were effective in increasing protection in intrarectal challenges. [167] Af-ter three intrarectal challenges, all the ten controls were infected, while only three and four out of ten were infected in the two respective vaccinated macaque groups.…”

Section: Hiv Vaccinesmentioning

confidence: 99%

Pharmaceutical Approaches to HIV Treatment and Prevention

Yavuz

Morgan

Showalter

et al. 2018

Advanced Therapeutics

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Human immunodeficiency virus (HIV) infection continues to pose a major infectious disease threat worldwide. It is characterized by the depletion of CD4 + T cells, persistent immune activation, and increased susceptibility to secondary infections. Advances in the development of antiretroviral drugs and combination antiretroviral therapy have resulted in a remarkable reduction in HIV-associated morbidity and mortality. Antiretroviral therapy (ART) leads to effective suppression of HIV replication with partial recovery of host immune system and has successfully transformed HIV infection from a fatal disease to a chronic condition. Additionally, antiretroviral drugs have shown promise for prevention in HIV pre-exposure prophylaxis and treatment as prevention. However, ART is unable to cure HIV. Other limitations include drug-drug interactions, drug resistance, cytotoxic side effects, cost, and adherence. Alternative treatment options are being investigated to overcome these challenges including discovery of new molecules with increased anti-viral activity and development of easily administrable drug formulations. In light of the difficulties associated with current HIV treatment measures, and in the continuing absence of a cure, the prevention of new infections has also arisen as a prominent goal among efforts to curtail the worldwide HIV pandemic. In this review, the authors summarize currently available anti-HIV drugs and their combinations for treatment, new molecules under clinical development and prevention methods, and discuss drug delivery formats as well as associated challenges and alternative approaches for the future.

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Induction of vaginal-resident HIV-specific CD8 T cells with mucosal prime–boost immunization

Cited by 41 publications

References 67 publications

Tissue-resident lymphocytes: from adaptive to innate immunity

Tissue-resident lymphocytes: from adaptive to innate immunity

Tissue‐resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance

Pharmaceutical Approaches to HIV Treatment and Prevention

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