| 1. |
- Akeus, Paulina, et al.
(author)
-
Regulatory T cells control endothelial chemokine production and migration of T cells into intestinal tumors of APC(min/+) mice
- 2018
-
In: Cancer Immunology Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 67:7, s. 1067-1077
-
Journal article (peer-reviewed)abstract
- Tumor-infiltrating lymphocytes are crucial for anti-tumor immunity. We have previously shown that regulatory T cells (Treg) are able to reduce T-cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo. Treg depletion also resulted in increased levels of the chemokines CXCL9 and CXCL10 specifically in the tumors. In this study, we investigated the mechanisms for Treg mediated suppression of T-cell migration into intestinal tumors in the APC(min/+) mouse model. By breeding APC(min/+) mice with DEREG mice, which harbour a high affinity diphtheria toxin receptor under the control of the FOXP3 promoter, we were able to deplete Treg in tumor-bearing mice. Using adoptive transfer experiments, we could document a markedly increased migration of T cells specifically into Treg depleted tumors, and that Treg depletion results in increased production of the CXCR3 ligand CXCL10 from endothelial cells in the tumors. Furthermore, we were able to demonstrate that T cells use CXCR3 to migrate into intestinal tumors. In addition, human colon adenocarcinomas express high levels of mRNA CXCR3 ligands and tumor endothelial cells produce CXCL9 and CXCL10 ex vivo. In conclusion, this study demonstrates that Treg reduce endothelial CXCL10 production, inhibit T-cell migration into tumors and that CXCR3 mediated signalling is crucial for lymphocyte accumulation in intestinal tumors. Thus, immunotherapy aimed at Treg depletion may be effective by increasing not only T effector cell activity, but also their accumulation in tumors.
|
|
| 2. |
- Alsén, Samuel, et al.
(author)
-
Antigen-Presenting B Cells Program the Efferent Lymph T Helper Cell Response
- 2022
-
In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
-
Journal article (peer-reviewed)abstract
- B cells interact with T follicular helper (Tfh) cells in germinal centers (GCs) to generate high-affinity antibodies. Much less is known about how cognate T-B-cell interactions influence Th cells that enter circulation and peripheral tissues. Therefore, we generated mice lacking MHC-II expressing B cells and, by thoracic duct cannulation, analyzed Th cells in the efferent lymph at defined intervals post-immunization. Focusing on gut-draining mesenteric lymph nodes (MLNs), we show that antigen-specific alpha(4)beta(+)(7) gut-homing effector Th cells enter the circulation prior to CXCR5(+)PD-1(+) Tfh-like cells. B cells appear to have no or limited impact on the early generation and egress of gut-homing Th cells but are critical for the subsequent appearance of Tfh-like cells that peak in the lymph before GCs have developed. At this stage, antigen-presenting B cells also reduce the proportion of alpha(4)beta(+)(7) Th cells in the MLN and efferent lymph. Furthermore, cognate B-cell interaction drives a broad transcriptional program in Th cells, including IL-4 that is confined to the Tfh cell lineage. The IL-4-producing Tfh-like cells originate from Bcl6(+) precursors in the LNs and have gut-homing capacity. Hence, B cells program the efferent lymph Th cell response within a limited window of time after antigenic challenge.
|
|
| 3. |
- Dahlgren, Madelene, et al.
(author)
-
T Follicular Helper, but Not Th1, Cell Differentiation in the Absence of Conventional Dendritic Cells
- 2015
-
In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 194:11, s. 5187-5199
-
Journal article (peer-reviewed)abstract
- Development of long-lived humoral immunity is dependent on CXCR5-expressing T follicular helper (Tfh) cells, which develop concomitantly to effector Th cells that support cellular immunity. Conventional dendritic cells (cDCs) are critical APCs for initial priming of naive CD4(+) T cells but, importantly, also provide accessory signals that govern effector Th cell commitment. To define the accessory role of cDCs during the concurrent development of Tfh and effector Th1 cells, we performed high-dose Ag immunization in conjunction with the Th1-biased adjuvant polyinosinic: polycytidylic acid (pI:C). In the absence of cDCs, pI: C failed to induce Th1 cell commitment and IgG2c production. However, cDC depletion did not impair Tfh cell differentiation or germinal center formation, and long-lived IgG1 responses of unaltered affinity developed in mice lacking cDCs at the time point for immunization. Thus, cDCs are required for the pI: C-driven Th1 cell fate commitment but have no crucial accessory function in relation to Tfh cell differentiation.
|
|
| 4. |
- Dahlin, Christer, 1959, et al.
(author)
-
Apical peri-implantitis: possible predisposing factors, case reports, and surgical treatment suggestions.
- 2009
-
In: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 11:3, s. 222-7
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Apical peri-implantitis is often diagnosed by clinical findings such as pain, redness, tenderness, swelling, and sometimes the presence of a fistulous tract. There are few theories about how such a lesion occurs. Hence, the current clinical treatment protocols are scanty. PURPOSE: The aim of this report was to evaluate and confer a more extended surgical protocol and to discuss possible predisposing factors for the development of retrograde peri-implantitis. MATERIALS AND METHODS: Two patients were extensively evaluated with regard to clinical signs, implant treatment, postoperative complications, and surgical treatment. The surgical protocol comprised debridement, with the additional removal of the apical portion of the affected implant. Postoperative checkup included clinical examination and radiographs. The follow-up period ranged from 1 to 3 years following surgical debridement. The possible predisposing factors are also discussed in the article. RESULTS: Both cases healed uneventfully with no further symptoms. Radiographs revealed complete bone fill into the resected area and continuous stable bone levels around the previously affected implants. CONCLUSIONS: It is concluded that recommendations for treatment of apical peri-implantitis are still minimal. In the present study, a surgical approach with resection of the apical portion of the affected implants in combination with debridement is suggested. Our experience was that partially resected oral implants remain osseointegrated and also function well clinically with a follow-up period up to 3 years.
|
|
| 5. |
- Hossein, Kashani, et al.
(author)
-
Influence of different prophylactic antibiotic regimens on implant survival rate: A retrospective clinical study
- 2005
-
In: CLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH. - : Wiley. - 1523-0899 .- 1708-8208. ; 7:1, s. 32-35
-
Journal article (peer-reviewed)abstract
- Background: The routine use of antibiotics in oral implant treatment seems to be widespread. The pre- or postoperative use of antibiotics in conjunction with implant surgery and its correlation with failure and success rates are poorly documented in the literature. The debate regarding overprescription of antibiotics raises the need for a critical evaluation of proper antibiotic coverage in association with implant treatment. Purpose: The purpose of this study was to compare the implant survival rate following a 1-day single-dose preoperative antibiotic regimen with that following a 1-week postoperative antibiotic protocol. Materials and Methods: The study included 868 consecutively treated patients. A total of 3,021 implants were placed. The population was split into two categories, either receiving a 1-day single-dose administration only, or a 1-week postoperative administration of antibiotics. Healing was evaluated at second-stage surgery (6 months for the upper jaw, 3 months for the lower jaw). Failure was defined as removal of implants because of non-osseointegration. Statistical analyses were performed with analysis of variance and the Scheffe test, with a significance level of 5% for comparison of data. Results: No significant differences with regard to complications and implant survival were found in the study. Conclusion: Based on the present data, a more restrictive regimen consisting of a 1-day dose of prophylactic antibiotic in conjunction with routine implant procedures is recommended.
|
|
| 6. |
- Sundström, Patrik, et al.
(author)
-
Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but Produce Reduced Amounts of IFN-γ.
- 2015
-
In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 195:7, s. 3472-3481
-
Journal article (peer-reviewed)abstract
- Mucosa-associated invariant T (MAIT) cells are innate-like T cells with a conserved TCR α-chain recognizing bacterial metabolites presented on the invariant MHC-related 1 molecule. MAIT cells are present in intestinal tissues and liver, and they rapidly secrete IFN-γ and IL-17 in response to bacterial insult. In colon cancer, IL-17-driven inflammation promotes tumor progression, whereas IFN-γ production is essential for antitumor immunity. Thus, tumor-associated MAIT cells may affect antitumor immune responses by their secreted cytokines. However, the knowledge of MAIT cell presence and function in tumors is virtually absent. In this study, we determined the frequency, phenotype, and functional capacity of MAIT cells in colon adenocarcinomas and unaffected colon lamina propria. Flow cytometric analyses showed significant accumulation of MAIT cells in tumor tissue, irrespective of tumor stage or localization. Colonic MAIT cells displayed an activated memory phenotype and expression of chemokine receptors CCR6 and CCR9. Most MAIT cells in unaffected colon tissues produced IFN-γ, whereas only few produced IL-17. Colonic MAIT cells also produced TNF-α, IL-2, and granzyme B. In the tumors, significantly lower frequencies of IFN-γ-producing MAIT cells were seen, whereas there were no differences in the other cytokines analyzed, and in vitro studies showed that secreted factors from tumor tissue reduced IFN-γ production from MAIT cells. In conclusion, MAIT cells infiltrate colon tumors but their ability to produce IFN-γ is substantially reduced. We suggest that MAIT cells have the capacity to promote local immune responses to tumors, but factors in the tumor microenvironment act to reduce MAIT cell IFN-γ production.
|
|
