scholarly journals IL-10 Directly Activates and Expands Tumor-Resident CD8+ T Cells without De Novo Infiltration from Secondary Lymphoid Organs

2012 ◽  
Vol 72 (14) ◽  
pp. 3570-3581 ◽  
Author(s):  
Jan Emmerich ◽  
John B. Mumm ◽  
Ivan H. Chan ◽  
Drake LaFace ◽  
Hoa Truong ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
De Novo ◽  
Lymphoid Organs ◽  
Secondary Lymphoid Organs

scholarly journals Early age-related atrophy of cutaneous lymph nodes precipitates an early functional decline in skin immunity in mice with aging

2021 ◽  
Author(s):  
Sandip Ashok Sonar ◽  
Jennifer L Uhrlaub ◽  
Christopher P Coplen ◽  
Gregory D Sempowski ◽  
Jarrod A Dudakov ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
De Novo ◽  
Functional Decline ◽  
Lymphoid Organs ◽  
Reticular Cell ◽  
Effector Cells ◽  
Age Related ◽  
Secondary Lymphoid Organs

Secondary lymphoid organs (SLO; including the spleen and lymph nodes) are critical both for the maintenance of naive T (TN) lymphocytes and for the initiation and coordination of immune responses. How they age, including the exact timing, extent, physiological relevance, and the nature of age-related changes, remains incompletely understood. We used time-stamping to indelibly mark cohorts of newly generated naive T cells (a.k.a. recent thymic emigrants - RTE) in mice, and followed their presence, phenotype and retention in SLO. We found that SLO involute asynchronously. Skin-draining lymph nodes (LN) atrophied early (6-9 months) in life and deeper tissue-draining LN and the spleen late (18-20 months), as measured by the loss of both TN numbers and the fibroblastic reticular cell (FRC) network. Time-stamped RTE cohorts of all ages entered SLO and successfully completed post-thymic differentiation. However, in older mice, these cells were poorly retained, and those found in SLO exhibited an emigration phenotype (CCR7loS1P1hi). Transfers of adult RTE into recipients of different ages formally demonstrated that the defect segregates with the age of the SLO microenvironment and not with the age of T cells. Finally, upon intradermal immunization, RTE generated in mice as early as 6-7 months of age barely participated in de novo immune responses and failed to produce well-armed effector cells. These results highlight changes in structure and function of superficial secondary lymphoid organs in laboratory mice that are earlier than expected and are consistent with the long-appreciated and pronounced reduction of cutaneous immunity with aging.

The Lymphoid Chemokine CCL21 Enhances the Migration- and CTL-Inducing Functions of Dendritic Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1127-1127
Author(s):  
Cheol Yi Hong ◽  
Pawel Kalinski ◽  
Hyeoung-Joon Kim ◽  
Je-Jung Lee
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Dependent Manner ◽  
Migratory Capacity ◽  
Secondary Lymphoid Organs

Abstract Abstract 1127 The migration of dendritic cells (DCs) to secondary lymphoid organs is very important to elicit an adaptive immune response in cancer immunotherapy. Here, we show the effect of lymphoid cytokine on the ability of maturing DCs to migrate in response to the lymph node-associated chemokines. The secondary-lymphoid organ chemokine (SLC/CCL21) during DC maturation dramatically enhanced DC migratory capacity responding to CCL21 and CCL19, and, moreover, produced strongly enhanced cytotoxic T cells, although it did not affect the expression of cell surface markers such as CD80, CD83, CD86, and CCR7 and the production of cytokines such as IL-12p70, IL-10, and IL-23. Mature DCs (mDCs) exposed by chemokine produced higher levels of CXCL10 (IP-10) that is one of the chemokines involved in Th1 attraction, but did not affect the production of Th2-attracting cytokine CCL22, compared with unstimulated mDCs. CCL21-exposed DCs induced strongly enhanced numbers of the interferon-g (IFN-g)-expressing antigen-specific CD8+ T cells against tumor-specific antigens in an CXCL10-dependent manner. Cytotoxic CD8+ T cells stimulated with CCL21-exposed DCs expressed higher level of IFN-g than those stimulated with control mDCs. Interestingly, generation of cytotoxic T cells (CTLs) stimulated by TNFa/IL-1b/IL-6/PGE2-treated DCs (sDCs) supplemented with IP-10 produced strong cytotoxic T cells expressing higher level of IFN-g. Tetramer assay showed that CCL21-treated DCs enhanced generation of antigen-specific CTLs. Taken together, our data suggest that mDCs pre-stimulated by chemokine CCL21 enhanced migratory capacity to secondary lymphoid organs and produced strong cytotoxic T cells via IP-10 signaling pathway. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CXCL12 Mediates CCR7-independent Homing of Central Memory Cells, But Not Naive T Cells, in Peripheral Lymph Nodes

2004 ◽  
Vol 199 (8) ◽  
pp. 1113-1120 ◽  
Author(s):  
M. Lucila Scimone ◽  
Thomas W. Felbinger ◽  
Irina B. Mazo ◽  
Jens V. Stein ◽  
Ulrich H. von Andrian ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Lymphoid Organs ◽  
Central Memory ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Peripheral Lymph ◽  
Secondary Lymphoid Organs

Central memory CD8+ T cells (TCM) confer superior protective immunity against infections compared with other T cell subsets. TCM recirculate mainly through secondary lymphoid organs, including peripheral lymph nodes (PLNs). Here, we report that TCM, unlike naive T cells, can home to PLNs in both a CCR7-dependent and -independent manner. Homing experiments in paucity of lymph node T cells (plt/plt) mice, which do not express CCR7 ligands in secondary lymphoid organs, revealed that TCM migrate to PLNs at ∼20% of wild-type (WT) levels, whereas homing of naive T cells was reduced by 95%. Accordingly, a large fraction of endogenous CD8+ T cells in plt/plt PLNs displayed a TCM phenotype. Intravital microscopy of plt/plt subiliac lymph nodes showed that TCM rolled and firmly adhered (sticking) in high endothelial venules (HEVs), whereas naive T cells were incapable of sticking. Sticking of TCM in plt/plt HEVs was pertussis toxin sensitive and was blocked by anti-CXCL12 (SDF-1α). Anti-CXCL12 also reduced homing of TCM to PLNs in WT animals by 20%, indicating a nonredundant role for this chemokine in the presence of physiologic CCR7 agonists. Together, these data distinguish naive T cells from TCM, whereby only the latter display greater migratory flexibility by virtue of their increased responsiveness to both CCR7 ligands and CXCL12 during homing to PLN.

scholarly journals Cutting Edge: Resident Memory CD8 T Cells Occupy Frontline Niches in Secondary Lymphoid Organs

2014 ◽  
Vol 192 (7) ◽  
pp. 2961-2964 ◽  
Author(s):  
Jason M. Schenkel ◽  
Kathryn A. Fraser ◽  
David Masopust
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Lymphoid Organs ◽  
Cutting Edge ◽  
Memory Cd8 T Cells ◽  
Secondary Lymphoid Organs

scholarly journals EXTH-43. GENERATION OF A B-CELL-BASED VACCINE FOR THE TREATMENT OF GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii96-ii96
Author(s):  
Catalina Lee Chang ◽  
Jason Miska ◽  
David Hou ◽  
Aida Rashidi ◽  
Peng Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Cross Presentation ◽  
Control Tumor Growth ◽  
Efficient Alternative ◽  
Control Tumor ◽  
Secondary Lymphoid Organs

Abstract Immunotherapy has revolutionized the treatment of many tumors. However, most glioblastoma (GBM) patients have not, so far, benefited from such successes. With the goal of exploring ways to boost anti-GBM immunity, we developed a B-cell-based vaccine (BVax) that consists of 4-1BBL+ B cells activated with CD40 agonism and IFNg stimulation. BVaxmigrate to key secondary lymphoid organs and are proficient at antigen cross-presentation, which promotes both the survival and functionality of CD8+ T cells. A combination of radiation, BVax, and PD-L1 blockade conferred tumor eradication in 80% of treated tumor-bearing animals. This treatment elicited immunologic memory that prevented the growth of new tumors upon subsequent re-injection in cured mice. GBM patient-derived BVax were successful in activating autologous CD8+ T cells; these T cells showed a strong ability to kill autologous glioma cells. In addition to the role in activating CD8+ T cells, BVax produce tumor-specific antibodies able to control tumor growth via antibody-mediated cell cytotoxicity. In conclusion, BVax tackles GBM immunosurveillance escape by using both cellular (CD8+ T-cell activation) and humoral (anti-tumor antibody production) immunity. Our study provides an efficient alternative to current immunotherapeutic approaches that can be readily translated to the clinic.

Quantitation and visualization of tumor-specific T cells in the secondary lymphoid organs during and after tumor elimination by PET

2004 ◽  
Vol 31 (8) ◽  
pp. 1021-1031 ◽  
Author(s):  
Ken Matsui ◽  
Zheng Wang ◽  
Timothy J. McCarthy ◽  
Paul M. Allen ◽  
David E. Reichert
Keyword(s):  
T Cells ◽  
Lymphoid Organs ◽  
Secondary Lymphoid Organs

scholarly journals TAILORED DC INDUCE PROTECTIVE HIV-1 SPECIFIC POLYFUNCTIONAL CD8+ T CELLS IN THE LYMPHOID TISSUE FROM HUMANIZED BLT MICE

2021 ◽  
Author(s):  
Marta Calvet-Mirabent ◽  
Daniel T. Claiborne ◽  
Maud Deruaz ◽  
Serah Tanno ◽  
Carla Serra ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Lymphoid Tissue ◽  
White Pulp ◽  
Blt Mice ◽  
Secondary Lymphoid Organs ◽  
The Impact ◽  
Hiv 1

Effective function of CD8+ T cells and enhanced innate activation of dendritic cells (DC) in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of TBK1-primed DC inducing protective CD8+ T cell responses in lymphoid tissue and peripheral blood and their association with reduced HIV-1 disease progression in vivo in the humanized bone marrow, liver and thymus (hBLT) mouse model. A higher proportion of hBLT-mice vaccinated with TBK1-primed DC exhibited less severe CD4+ T cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to secondary lymphoid organs and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, TBK1-primed DC might be an useful tool for subsequent vaccine studies.

scholarly journals Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance

2016 ◽  
Vol 213 (13) ◽  
pp. 3057-3073 ◽  
Author(s):  
Shiki Takamura ◽  
Hideki Yagi ◽  
Yoshiyuki Hakata ◽  
Chihiro Motozono ◽  
Sean R. McMaster ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
De Novo ◽  
Memory T Cells ◽  
Tissue Injury ◽  
Effector Memory ◽  
Respiratory Pathogens ◽  
Damage Site ◽  
Memory Cd8 T Cells ◽  
Specific Localization

CD8+ tissue-resident memory T cells (TRM cells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8+ TRM cells in the lung, which physiologically consists of a markedly scant interstitium compared with other mucosa, remains unclear. In this study, we show that lung CD8+ TRM cells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissue-circulating CD8+ effector memory T cells (TEM cells) are widely but sparsely distributed in unaffected areas. Although CD69 inhibited sphingosine 1–phosphate receptor 1–mediated egress of CD8+ T cells immediately after their recruitment into lung tissues, such inhibition was not required for the retention of cells in the TRM niches. Furthermore, despite rigid segregation of TEM cells from the TRM niche, prime-pull strategy with cognate antigen enabled the conversion from TEM cells to TRM cells by creating de novo TRM niches. Such damage site–specific localization of CD8+ TRM cells may be important for efficient protection against secondary infections by respiratory pathogens.

Sign in / Sign up

Export Citation Format

Share Document