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 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

Allogeneic Environment and Tissue Damage Provide Critical Stimuli for Regulatory T Cell Expansion and Survival In Vivo after Hematopoietic Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1731-1731
Author(s):  
Vu H. Nguyen ◽  
Daisy Chang ◽  
Robert S. Negrin
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Tissue Damage ◽  
Hematopoietic Cell Transplantation ◽  
Critical Role ◽  
Lymphoid Organs ◽  
Gamma Chain ◽  
Secondary Lymphoid Organs

Abstract CD4+CD25+ regulatory T cells (Treg) mediate alloresponses in murine models of bone marrow transplantation (BMT), leading to protection from graft-versus-host disease (GvHD). However, in vivo migration and tissue localization of Treg during this inflammatory response remain unclear. We previously demonstrated co-localization of Treg with effector T cells (Tcon) with initial expansion in secondary lymphoid organs prior to migration into inflamed tissues in a major MHC-mismatched BMT model. To explore the stimuli for Treg proliferation, we evaluated the role of the allogeneic environment by transferring FVB donor luciferase-expressing (luc+) Treg into lethally-irradiated syngeneic recipients. Unlike the allogeneic irradiated setting where Treg expand in the presence or absence of Tcon, adoptively transferred luc+ Treg were not detected in secondary lymphoid organs of syngeneic lethally-irradiated BMT recipients by in vivo bioluminescence imaging (BLI). Syngeneic luc+ Tcon also had significantly different in vivo dynamics, with a 4 day delay and only moderate expansion in lymph nodes. Proliferation was not detected in the spleen, unlike their allogeneic Tcon counterparts, nor in the bone marrow compartments, as seen in lymphopenic models. To assess whether irradiation induced the observed in vivo dynamics of Treg in the allogeneic setting, we transferred FVB luc+ Treg or luc+ Tcon into unirradiated Balb/c Rag2−/−gamma chain (γC) −/− recipients, which lack T, B, and NK cells. After adoptive transfer into Rag2−/−γC−/− recipients, robust Tcon proliferation was observed in secondary lymphoid organs and the bone marrow compartments; however, Treg expansion was weak, and specific localization to lymphoid or nonlymphoid tissues was not observed. Treg were stimulated to localize to and expand in secondary lymphoid organs by the co-transfer of Tcon in unirradiated Rag2−/− (γC) −/− or by conditioning Rag2−/− (γC) −/− recipients with irradiation. Exogenous IL2 administration two weeks following luc+ Treg transfer into unirradiated Rag2−/− (γC) −/− recipients similarly led to localization and expansion of Treg in secondary lymphoid organs. These studies indicate the critical role of proinflammatory cytokines, such as IL2, generated either by irradiation-induced tissue damage or donor Tcon, in the expansion and localization of Treg. Differences between Tcon and Treg expansion in syngeneic or unconditioned allogeneic Rag2−/− γC−/− hosts suggest an important role of conditioning with irradiation alone or in concert with the allogeneic environment, in providing distinct signals for Tcon versus Treg activation, proliferation, and localization.

scholarly journals Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples

2021 ◽  
Vol 22 (21) ◽  
pp. 11497
Author(s):  
Brigitte Sibille ◽  
Isabelle Mothe-Satney ◽  
Gwenaëlle Le Menn ◽  
Doriane Lepouse ◽  
Sébastien Le Garf ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Exercise Training ◽  
Lymphoid Organs ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Blood Samples ◽  
Secondary Lymphoid Organs ◽  
Vitro Effect ◽  
Receptor Beta

Synthetic ligands of peroxisome-proliferator-activated receptor beta/delta (PPARβ/δ) are being used as performance-enhancing drugs by athletes. Since we previously showed that PPARβ/δ activation affects T cell biology, we wanted to investigate whether a specific blood T cell signature could be employed as a method to detect the use of PPARβ/δ agonists. We analyzed in primary human T cells the in vitro effect of PPARβ/δ activation on fatty acid oxidation (FAO) and on their differentiation into regulatory T cells (Tregs). Furthermore, we conducted studies in mice assigned to groups according to an 8-week exercise training program and/or a 6-week treatment with 3 mg/kg/day of GW0742, a PPARβ/δ agonist, in order to (1) determine the immune impact of the treatment on secondary lymphoid organs and to (2) validate a blood signature. Our results show that PPARβ/δ activation increases FAO potential in human and mouse T cells and mouse secondary lymphoid organs. This was accompanied by increased Treg polarization of human primary T cells. Moreover, Treg prevalence in mouse lymph nodes was increased when PPARβ/δ activation was combined with exercise training. Lastly, PPARβ/δ activation increased FAO potential in mouse blood T cells. Unfortunately, this signature was masked by training in mice. In conclusion, beyond the fact that it is unlikely that this signature could be used as a doping-control strategy, our results suggest that the use of PPARβ/δ agonists could have potential detrimental immune effects that may not be detectable in blood samples.

ICOS Costimulation Differentially Affects T Cells in Secondary Lymphoid Organs and Inflamed Tissues

2018 ◽  
Vol 59 (4) ◽  
pp. 437-447 ◽  
Author(s):  
Dana Vu Van ◽  
Laura Bauer ◽  
Richard A. Kroczek ◽  
Andreas Hutloff
Keyword(s):  
T Cells ◽  
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.

scholarly journals Interleukin-23 deficiency alters thymic selection in lupus-prone mice

Lupus ◽  
2019 ◽  
Vol 28 (8) ◽  
pp. 1007-1012
Author(s):  
H Dai ◽  
V C Kyttaris
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Polarization ◽  
Lymphoid Organs ◽  
Thymic Selection ◽  
Wild Type ◽  
Thymic Development ◽  
T Cell Polarization ◽  
Interleukin 23 ◽  
Secondary Lymphoid Organs

We have previously reported that IL-23 receptor deficiency in MRL. lpr mice ameliorates lupus by altering the balance of pro- and anti-inflammatory cytokines in secondary lymphoid organs. As IL-23 may also impact thymic selection, we evaluated the effect of IL-23 on thymic T cell development in lupus-prone mice. We generated IL-23p19-deficient MRL. lpr mice and harvested their thymus at 8 weeks of age. We found that the late stage double negative DN4 population was increased in IL-23p19–/– MRL. lpr mice when compared to IL-23p19+/+ MRL. lpr mice. Despite this, mature thymocytes (CD24–TCRβ+) were decreased by more than 50% in the IL-23p19-deficient mice versus wild-type controls. This was associated with a decrease in the generation of CD8+ T cells, possibly through downregulation of the IL-7 receptor. CD8+ T cells were not only fewer in numbers but also had decreased expression of the migration-related receptors CD44 and CD62L in the thymus and spleens of IL-23p19-deficient versus wild-type mice. We propose that IL-23 promotes the development of lupus-like autoimmunity not only through T cell polarization and cytokine production in the peripheral lymphoid organs but also by influencing T cell thymic development.

Expression of CCR9 β-chemokine receptor is modulated in thymocyte differentiation and is selectively maintained in CD8+ T cells from secondary lymphoid organs

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 850-857 ◽  
Author(s):  
Laura Carramolino ◽  
Ángel Zaballos ◽  
Leonor Kremer ◽  
Ricardo Villares ◽  
Pilar Martı́n ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Subset ◽  
Lymphoid Organs ◽  
Thymocyte Development ◽  
Double Positive ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Ccr9 Expression ◽  
Single Positive ◽  
Secondary Lymphoid Organs

Abstract Chemokines appear to have an important role in the seeding of lymphoid progenitors in the thymus, the regulation of the coordinated movements of the maturing T cells within this organ, and the egress of the resulting naive T cells to secondary lymphoid organs. CCR9, the specific receptor for the β-chemokine TECK/CCL25, is selectively expressed in thymus, lymph node, and spleen. Using a specific anti-CCR9 polyclonal antibody, K629, and a semiquantitative reverse transcriptase–polymerase chain reaction procedure, a detailed study of CCR9 expression in the thymus and secondary lymphoid organs was performed. The results show that CD4+CD8+ double-positive thymocytes have the highest CCR9 expression in thymus. Single-positive CD8+ thymocytes continue to express this receptor after abandoning the thymus as mature naive T cells, as suggested by the existence of a CD8+CD69lowCD62LhighCCR9+ cell subset. Consistent with this, CD8+lymphocytes from lymph nodes, spleen, and Peyer patches express a functional CCR9, as its expression correlates with migration in response to CCL25. Conversely, CD4+ thymocytes lose CCR9 before abandoning the thymus, and CD4+ T cells from secondary lymphoid organs also lack CCR9 expression. Analysis of CCR9 expression in thymocytes from mice of different ages showed that CCR9 levels are affected by age, as this receptor is more abundant, and its response to CCL25 is more potent in newborn animals. Collectively, these results suggest that CCR9 has a role in thymocyte development throughout murine life, with clear differences between the CD4+ and CD8+ lineages.

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.

Sign in / Sign up

Export Citation Format

Share Document