Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance

Osborn, Jossef F.; Hobbs, Samuel J.; Mooster, Jana L.; Khan, Tahsin N.; Kilgore, Augustus M.; Harbour, Jake C.; Nolz, Jeffrey C.

doi:10.1371/journal.ppat.1007633

Cited by 47 publications

(50 citation statements)

References 54 publications

(76 reference statements)

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“…Memory CD8 + T cells are antigen-experienced cells that show an improved response to second challenge, in comparison to naive cells. The relation of central memory CD8 + T cells and effector CD8 + T cells detected in the skin during inflammation has been established in CHS model as well as in viral infection (Gaide et al, 2015, Mbitikon-Kobo et al, 2009, Osborn et al, 2019. Our data demonstrate that expression of Gal-1 controls the generation of central memory CD8 + T cells, and the secretion of IFNγ, which account for the exacerbated skin inflammation.…”

Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 56%

Galectin-1 Expression in CD8+ T Lymphocytes Controls Inflammation in Contact Hypersensitivity

Castillo-González

Cibrián

Fernández‐Gallego

et al. 2021

Journal of Investigative Dermatology

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Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 56%

Galectin-1 Expression in CD8+ T Lymphocytes Controls Inflammation in Contact Hypersensitivity

Castillo-González

Cibrián

Fernández‐Gallego

et al. 2021

Journal of Investigative Dermatology

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“…Data from other models show that T RM cells display variable phenotypes during infection with different pathogens. One report showed that T CM cells trafficked to the skin during vaccinia virus infection and converted to CD69 + T RM cells, without CD103 expression (48). Lymphoid T RM cells displayed a similar phenotype during recovery from LCMV infection (19).…”

Section: Discussionmentioning

confidence: 99%

Immunity to Respiratory Infection Is Reinforced Through Early Proliferation of Lymphoid TRM Cells and Prompt Arrival of Effector CD8 T Cells in the Lungs

et al. 2019

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Cross-protection between serologically distinct strains of influenza A virus (IAV) is mediated by memory CD8 T cells that recognize epitopes from conserved viral proteins. Early viral control begins with activation of tissue-resident memory CD8 T cells (T RM ) cells at the site of viral replication. These CD8 T cells do not act in isolation, as protection against disseminated infection is reinforced by multiple waves of effector cells (T EFF ) that enter the lungs with different kinetics. To define how a protective CTL response evolves, we compared the functional properties of antiviral CD8 T cells in the respiratory tract and local lymphoid tissues. When analyzed 30 dpi, large numbers of antiviral CD8 T cells in the lungs and mediastinal lymph nodes (MLNs) expressed canonical markers of T RM cells (CD69 and/or CD103). The check point inhibitor PD-1 was also highly expressed on NP-specific CD8 T cells in the lungs, while the ratios of CD8 T cells expressing CD69 and CD103 varied according to antigen specificity. We next used in vitro experiments to identify conditions that induce a canonical T RM phenotype and found that that naïve and newly activated CD8 T cells maintain CD103 expression during culture with transforming growth factor-beta (TGFβ), while central memory CD8 T cells (T CM ) do not express CD103 under similar conditions. In vivo experiments showed that the distribution of antiviral CTLs in the MLN changed when immune mice were treated with reagents that block interactions with PD-L1. Importantly, the lymphoid T RM cells were poised for early proliferation upon reinfection with a different strain of IAV and defenses in the lungs were augmented by a transient increase in numbers of T EFF cells at the site of infection. As the interval between infections increased, lymphoid T RM cells were replaced with T CM cells which proliferated with delayed kinetics and contributed to an exaggerated inflammatory response in the lungs.

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“…22 Moreover, central memory CD8 T cells can also traffic into tissues and can become tissue resident cells and provide improved tissue METFORMIN ON HIV-SPECIFIC T CELL TO PD-L1 BLOCKADE surveillance in shock and kill HIV remission strategies. 23 Our observations of increased central memory population CD8 T cells may have a beneficial effect on improving HIV-specific CD8 T cell responses.…”

Section: Discussionmentioning

confidence: 75%

Effects of Brief Adjunctive Metformin Therapy in Virologically Suppressed HIV-Infected Adults on Polyfunctional HIV-Specific CD8 T Cell Responses to PD-L1 Blockade

Chew

Padua

Chow

et al. 2021

AIDS Research and Human Retroviruses

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Targeting inhibitory immune checkpoint receptor pathways has shown remarkable success in improving anticancer T cell responses for the elimination of tumors. Such immunotherapeutic strategies are being pursued for HIV remission. Metformin has shown favorable clinical outcomes in enhancing the efficacy of programmed cell death-1 (PD-1) blockade and restoring antitumor T cell immunity. Furthermore, monocytes are known to be a strong predictor of progression-free survival in response to anti-PD-1 immunotherapy. In a single-arm clinical trial, we evaluated the immunological effects over an 8-week course of metformin therapy in seven euglycemic, virally suppressed HIV-infected participants on combination antiretroviral therapy (cART). We assessed changes in peripheral HIV-Gag-specific T cell responses to immune checkpoint blockade (ICB) with anti-PD-L1 and anti-T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) monoclonal antibodies (mAbs) and changes in CD8 T cell and monocyte subsets using flow cytometry. Study participants were all male, 71% (5/7) Caucasian, with a median age of 61 years, CD4 count of 739 cells/lL, and plasma HIV RNA of <50 copies/mL on stable cART for >1 year. Ex vivo polyfunctional HIV-Gag-specific CD8 T cell responses to anti-PD-L1 mAb significantly improved (p < .05) over the 8-week course of metformin therapy. Moreover, frequencies of both intermediate (CD14 + CD16 + ; r = 0.89, p = .01) and nonclassical (CD14 low CD16 + ; r = 0.92, p = .01) monocytes at entry were predictive of the magnitude of the anti-HIV CD8 T cell responses to PD-L1 blockade. Collectively, these findings highlight that 8-week course of metformin increases the polyfunctionality of CD8 T cells and that baseline monocyte subset frequencies may be a potential determinant of PD-L1 blockade efficacy. These data provide valuable information for HIV remission trials that utilize ICB strategies to enhance anti-HIV CD8 T cell immunity.

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Central memory CD8+ T cells become CD69+ tissue-residents during viral skin infection independent of CD62L-mediated lymph node surveillance

Cited by 47 publications

References 54 publications

Galectin-1 Expression in CD8+ T Lymphocytes Controls Inflammation in Contact Hypersensitivity

Galectin-1 Expression in CD8+ T Lymphocytes Controls Inflammation in Contact Hypersensitivity

Immunity to Respiratory Infection Is Reinforced Through Early Proliferation of Lymphoid TRM Cells and Prompt Arrival of Effector CD8 T Cells in the Lungs

Effects of Brief Adjunctive Metformin Therapy in Virologically Suppressed HIV-Infected Adults on Polyfunctional HIV-Specific CD8 T Cell Responses to PD-L1 Blockade

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