L-selectin Is Essential for Delivery of Activated CD8 + T Cells to Virus-Infected Organs for Protective Immunity

Mohammed, Rebar N.; Watson, H. Angharad; Vigar, Miriam Ann; Ohme, Julia; Thomson, Amanda; Humphreys, Ian R.; Ager, Ann

doi:10.1016/j.celrep.2015.12.090

Cited by 44 publications

(78 citation statements)

References 40 publications

(43 reference statements)

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“…While both phenotypic Tcell markers are used to characterize na€ ıve T cells 32 and are crucial for homing to secondary lymphoid tissue, CD62L also directs cells to inflamed tissues. 47,48 After aAPC stimulation, our CB CTLs lost their CD62L expression, whereas PB CTLs maintained or slightly increased CD62L expression. This emphasizes that antigen-specific CD45RA1CCR71CD62L-CB CTLs maintain their homing potential, remain in secondary lymphoid tissue, and mediate antitumor effects, whereas CD45RA-CCR7-CD62L1 PB CTLs are more likely to travel to inflamed tissues, which might further lead to possibly antigenmediated GVHD induction.…”

Section: Discussionmentioning

confidence: 88%

Cord blood–derived T cells allow the generation of a more naïve tumor‐reactive cytotoxic T‐cell phenotype

et al. 2017

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BACKGROUND Transplantation of hematopoietic stem cells (HSCs) from peripheral blood (PB) or cord blood (CB) is well established. HSCs from CB are associated with a lower risk of graft‐versus‐host disease (GVHD), but antigen‐independent expanded CB‐ and PB‐derived T cells can induce GVHD in allo‐HSC recipients. CB‐derived cells might be more suitable for adoptive immunotherapy as they have unique T‐cell characteristics. Here, we describe functional differences between CB and PB T cells stimulated with different cytokine combinations involved in central T‐cell activation. STUDY DESIGN AND METHODS Isolated CD8+ T cells from CB and PB were stimulated antigen independently with anti‐CD3/CD28 stimulator beads or in an antigen‐dependent manner with artificial antigen‐presenting cells loaded with the HLA‐A*02:01‐restricted peptide of tumor‐associated melanoma antigen recognized by T cells 1 (MART1). CB and PB T cells cultured in the presence of interleukin (IL)‐7, IL‐15, IL‐12, and IL‐21 were characterized for T‐cell phenotype and specificity, that is, by CD107a, interferon‐γ, tumor necrosis factor‐α, and IL‐2 expression. RESULTS After antigen‐independent stimulation, activated CD8+ CB T cells exhibited stronger proliferation and function than those from PB. After antigenic stimulation, MART1‐reactive CB T cells were naïve (CD45RA+CCR7+), cytotoxic, and highly variable in expressing homing marker CD62L. Addition of IL‐21 resulted in increased T‐cell proliferation, whereas supplementation with IL‐12 decreased IL‐21–induced expansion, but increased the functionality and cytotoxicity of CB and PB T cells. CONCLUSION MART1‐reactive CB T cells with a more naïve phenotype and improved properties for homing can be generated. The results contribute to better understanding the effects on GVHD and graft versus tumor.

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Section: Discussionmentioning

confidence: 88%

Cord blood–derived T cells allow the generation of a more naïve tumor‐reactive cytotoxic T‐cell phenotype

et al. 2017

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“…L-selectin + of T cells, a type 1 membrane protein, regulates lymphocyte homing into peripheral lymph node and accumulates leukocytes in inflammation area 3,8,37 . This molecule is expressed by naïve T cells CD4 + L-selectin + and CD8 + L-selectin + .…”

Section: Discussionmentioning

confidence: 99%

Untitled

2018

IJPSR

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“…3D). Interestingly, a recent report shows that L-Selection/CD62L expression is important for the recruitment of activated CD8 + T cells to virus infected tissues for protective immunity [25]. In addition, a greater proportion of activated CD8 + T cells from IL-2 complex treated mice expressed CD122 (Fig.…”

Section: Resultsmentioning

confidence: 92%

IL-2 complex treatment amplifies CD8+ T cell mediated immunity following herpes simplex virus-1 infection

Rajasagi

Rouse

2016

Microbes and Infection

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CD8+ T cells play an important role in controlling numerous virus infections and some tumors and therefore several strategies have been adopted to modulate CD8+ T cell responses. One such approach includes treatment with IL-2 bound to a monoclonal antibody against IL-2 (IL-2 complex) which was shown to enhance CD8+ T cell responses and provide protection against some cancers and pathogens. This report analyses the value of IL-2 complex therapy to protect against a cutaneous virus infection as occurs with herpes simplex virus-1 (HSV-1) infection. Treatment with IL-2 complex after infection reduced virus levels and lesion severity in a zosteriform model of HSV infection in mice. Furthermore, IL-2 complex treatment expanded HSV-1-gB epitope-specific CD8+ T cells, IFN-γ and TNF-α producing CD8+ T cells as well as cells that produced more than one cytokine. In addition, IL-2 complex therapy recipients showed enhanced cytolytic activity of CD8+ T cells as shown by increased granzyme B expression and lytic granule release. Taken, together, these studies demonstrate that IL-2 complex therapy can be useful to boost protection against a cutaneous virus infection.

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L-selectin Is Essential for Delivery of Activated CD8 + T Cells to Virus-Infected Organs for Protective Immunity

Cited by 44 publications

References 40 publications

Cord blood–derived T cells allow the generation of a more naïve tumor‐reactive cytotoxic T‐cell phenotype

Cord blood–derived T cells allow the generation of a more naïve tumor‐reactive cytotoxic T‐cell phenotype

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IL-2 complex treatment amplifies CD8+ T cell mediated immunity following herpes simplex virus-1 infection

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