共查询到20条相似文献,搜索用时 75 毫秒
1.
Raffeiner B Dejaco C Duftner C Kullich W Goldberger C Vega SC Keller M Grubeck-Loebenstein B Schirmer M 《Arthritis research & therapy》2005,7(6):R1412-R1420
CD3+CD4+CD28null and CD3+CD8+CD28null T cells are enriched in patients with immune-mediated diseases compared with healthy controls. This study shows that CD4+CD28null T cells express Toll-like receptors recognizing bacterial lipopolysaccharides in ankylosing spondylitis, psoriatic arthritis
and rheumatoid arthritis. In ankylosing spondylitis, TLR4 (23.1 ± 21.9%) and, to a smaller extent, TLR2 (4.1 ± 5.8%) were
expressed on CD4+CD28null T cells, whereas expression was negligible on CD4+CD28+ and CD8+ T cells. CD4+CD28null T cells produced perforin upon stimulation with lipopolysaccharide, and this effect was enhanced by autologous serum or recombinant
soluble CD14. Perforin production could be prevented with blocking antibodies directed against CD14 or TLR4. Incubation of
peripheral blood mononuclear cells with tumour necrosis factor alpha led to an upregulation of TLR4 and TLR2 on CD4+CD28null T cells in vitro, and treatment of patients with antibodies specifically directed against tumour necrosis factor alpha resulted in decreased
expression of TLR4 and TLR2 on CD4+CD28null T cells in vivo. We describe here a new pathway for direct activation of cytotoxic CD4+ T cells by components of infectious pathogens. This finding supports the hypothesis that CD4+CD28null T cells represent an immunological link between the innate immune system and the adaptive immune system. 相似文献
2.
Michael Schirmer Christian Goldberger Reinhard Würzner Christina Duftner Karl-P Pfeiffer Johannes Clausen Günther Neumayr Albrecht Falkenbach 《Arthritis research & therapy》2001,4(1):71-8
Circulating CD8+ CD28- T cells were found to be expanded more in patients with ankylosing spondylitis than in an age-matched healthy population (41.2 ± 17.7% versus 18.6 ± 7.6%). The level of CD8+CD28- T cells was dependent on the disease status, but was independent of age. Most of the CD8+ CD28- T cells produced perforin after stimulation in vitro, in contrast to their CD8+CD28+ counterparts. From the clinical perspective, the percentage of the cytotoxic CD8+ CD28- T cells reflected a more severe course of disease, as it correlated with distinct movement restrictions, as well as the metrology score summarizing cervical rotation (in sitting position), chin-to-jugulum distance, thoracic Schober, chest expansion, and fingers-to-floor distance (P = 0.032). 相似文献
3.
Pawlik A Ostanek L Brzosko I Brzosko M Masiuk M Machalinski B Gawronska-Szklarz B 《Arthritis research & therapy》2003,5(4):R210-R213
Clonal expansion of CD4+CD28- T cells is a characteristic finding in patients with rheumatoid arthritis (RA). Expanded CD4+ clonotypes are present in the peripheral blood, infiltrate into the joints, and persist for years. CD4+CD28- T cells are oligoclonal lymphocytes that are rare in healthy individuals but are found in high percentages in patients with
chronic inflammatory diseases. The size of the peripheral blood CD4+CD28- T-cell compartment was determined in 42 patients with RA and 24 healthy subjects by two-color FACS analysis. The frequency
of CD4+CD28- T cells was significantly higher in RA patients than in healthy subjects. Additionally, the number of these cells was significantly
higher in patients with extra-articular manifestations and advanced joint destruction than in patients with limited joint
manifestations. The results suggest that the frequency of CD4+CD28- T cells may be a marker correlating with extra-articular manifestations and joint involvement. 相似文献
4.
David A Horwitz 《Arthritis research & therapy》2010,12(1):101
Various abnormalities in CD4+CD25+ regulatory T cells (Tregs) in systemic lupus erythematosus (SLE) include increased Foxp3+ cells that are CD25 negative. Barring methodological technical factors, these cells could be atypical Tregs or activated
non-Treg CD4+ cells that express Foxp3. Two groups have reached opposite conclusions that could possibly reflect the subjects studied.
One group studied untreated new-onset SLE and suggested that these T cells were mostly CD25-Foxp3+ non-Tregs. The other group studied patients with long-standing disease and suggested that these cells are mostly dysfunctional
Tregs. A third group reported increased Foxp3+CD4+CD25dim rather than CD25- cells in active SLE and these were also non-Tregs. Thus, it is likely that not all Foxp3+ T cells in SLE have protective suppressive activity. 相似文献
5.
CD4+CD28null T cells are present in increased numbers in the peripheral blood of patients with acute coronary syndrome. However, the triggers
of expansion of these cells are unclear. Susceptibility to coronary heart disease (CHD) is strongly associated with alleles
of human leukocyte antigen (HLA), but it is not equally strong in different human populations. The objective of the study
was to investigate association between CD4+CD28null T cells and HLA-DRB1 alleles. The HLA alleles were determined by polymerase chain reaction with sequence-specific primers
(PCR-SSP) method, in a group of CHD patients and control subjects from the same area. The number of CD4+CD28null T cells was measured using the flow cytometry technique. The HLA-DRB1*01 (RR = 4.705, P < 0.005) and DRB1*04 (RR = 3.554, P < 0.005) alleles showed the strongest association with CHD in the Chinese population, and increased numbers of CD4+CD28null T cells were found in association with HLA-DRB1*04 (17.1%) and DRB*01 (12.9%), while decreased numbers of CD4+CD28null T cells were present in subjects with DRB1*15 (0.8%). CHD in Chinese population is strongly associated with HLA-DRB1*01 and
DRB1*04 haplotypes, and formation of CD4+CD28null T cells was related to HLA-DRB1*01, DRB1*04, and DRB1*15 alleles. 相似文献
6.
Molhoek KR McSkimming CC Olson WC Brautigan DL Slingluff CL 《Cancer immunology, immunotherapy : CII》2009,58(6):867-876
Targeted molecular therapies inhibit proliferation and survival of cancer cells but may also affect immune cells. We have
evaluated the effects of Sirolimus and Sorafenib on proliferation and survival of lymphoid cell subsets. Both drugs were cytotoxic
to CD4+CD25high T cells, and were growth inhibitory for CD4+ and CD8+ T cells. Cytotoxicity depended on CD3/CD28 stimulation and was detectable within 12 h, with 80–90% of CD4+CD25high cells killed by 72 h. Cell death was due to apoptosis, based on Annexin V and 7AAD staining. Addition of IL-2 prevented the
apoptotic response to Sirolimus, potentially accounting for reports that Sirolimus can enhance proliferation of CD4+CD25high cells. These results predict that Sirolimus or Sorafenib would reduce CD4+CD25high cells if administered prior to antigenic stimulation in an immunotherapy protocol. However, administration of IL-2 protects
CD4+CD25high T cells from cytotoxic effects of Sirolimus, a response that may be considered in design of therapeutic protocols. 相似文献
7.
Bardos T Czipri M Vermes C Finnegan A Mikecz K Zhang J 《Arthritis research & therapy》2003,5(2):R106-R113
Accumulating evidence suggests that regulatory T cells play a crucial role in preventing autoimmunity. Recently, a naturally
occurring CD4+CD25+ T-cell subset that is anergic and also suppressive has been shown to suppress autoimmunity in several animal models. We used
proteoglycan-induced arthritis (PGIA) as a study model to investigate the role of the CD4+CD25+ regulatory T cells in autoimmune arthritis. There was no significant change in the percentage of CD4+CD25+ T cells during the immunization period when proteoglycan- or ovalbumin-immunized BALB/c and C57BL/6 mice were compared. An
adoptive transfer study showed that the CD4+CD25+ T cells did not protect severe combined immunodeficient mice from arthritis when they were cotransferred with splenocytes
from arthritic animals. Similarly, depletion of the CD4+CD25+ T cells did not enhance the onset of the disease or disease severity in severe combined immunodeficient mice. Moreover, CD28-deficient
mice, which have very few CD4+CD25+ T cells, were highly resistant to PGIA. These findings indicate that the CD4+CD25+ regulatory T cells may not play a critical role in controlling PGIA. 相似文献
8.
The identification and separation of small intestinal epithelial stem cells are still on the preliminary stage. In this study,
we planned to utilize immunohistochemistry, fluorescence-activated cell sorting (FACS) and RT-PCR to investigate the possibility
of CD133 and CD44 as markers of human small intestinal epithelial stem cells. The expressions of CD133, CD44 and Lgr5 were
studied by immunohistochemistry. Four subgroups of CD133+CD44+, CD133+CD44−, CD133−CD44+, CD133−CD44− were sorted out through FACS and the expression level of Lgr5 gene was measured by RT-PCR and polyacrylamide gel electropheresis (PAGE) with sliver stained. Ten cases of samples were
available for analyzing. By immunohistochemical staining, few cells with positive expressions of CD133, CD44 and Lgr5 were
distributed in the bottom of crypts with the expression locations somewhat overlapped. The average percentage of CD133+CD44+ cells was 0.0580 ± 0.0403%, while the corresponding contents of CD133+CD44− cells, CD133−CD44+ cells and CD133−CD44− cells were 0.4000 ± 0.1225%, 0.7000 ± 0.2646% and 76.5600 ± 3.5529% respectively. Ten times of positive expressions of Lgr5 were detected in the CD133+CD44+ groups, while 9/10, 8/10 and 4/10 times for CD133+CD44−, CD133−CD44+ and CD133−CD44− subgroups respectively. With the help of Quantityone 4.62 software, the densities of corresponding place to Lgr5 and reference gene were obtained. The density ratios of corresponding place to Lgr5 to reference gene were significant difference between subgroups (P < 0.001). By means of LSD method, the density ratios in CD133+CD44+ subgroups had statistical differences from the other subgroups (P < 0.05). We concluded CD133+CD44+ cells may be human small intestinal epithelial stem cells, which need further researches to confirm. 相似文献
9.
10.
CD4+CD25+Foxp3+ regulatory T (Treg) cells are believed to play an important role in suppressing autoimmunity and maintaining peripheral tolerance. How their survival is regulated in the periphery is less clear. Here we show that Treg cells express receptors for gamma chain cytokines and are dependent on an exogenous supply of these cytokines to overcome cytokine withdrawal apoptosis in vitro. This result was validated in vivo by the accumulation of Treg cells in Bim-/- and Bcl-2 tg mice which have arrested cytokine deprivation apoptosis. We also found that CD25 and Foxp3 expression were down-regulated in the absence of these cytokines. CD25+ cells from Scurfy mice do not depend on cytokines for survival demonstrating that Foxp3 increases their dependence on cytokines by suppressing cytokine production in Treg cells. Our study reveals that the survival of Treg cells is strictly dependent on cytokines and cytokine producing cells because they do not produce cytokines. Our study thus, demonstrates that different gamma chain cytokines regulate Treg homeostasis in the periphery by differentially regulating survival and proliferation. These findings may shed light on ways to manipulate Treg cells that could be utilized for their therapeutic applications. 相似文献
11.
Targeting interleukin-2 (IL-2) and/or agonist anti-CD40 antibody (Ab) into tumors represents an effective vaccination strategy
that avoids systemic toxicity and resolves treated-site tumors. Here, we examined IL-2 and/or anti-CD40 Ab-driven local versus
systemic T cell function and the installation of T cell memory. Single tumor studies showed that IL-2 induced a potent CD4+ and CD8+ T cell response that was limited to the draining lymph node and treated-site tumor, and lymph node tumor-specific CD8+ T cells did not upregulate CD44. A two-tumor model showed that while IL-2-treated-site tumors resolved, distal tumors continued
to grow, implying limited systemic immunity. In contrast, anti-CD40 Ab treatment with or without IL-2 expanded the systemic
T cell response to non-draining lymph nodes, and distal tumors resolved. Tumor-specific T cells in lymph nodes of anti-CD40
Ab ± IL-2-treated mice upregulated CD44, demonstrating activation and transition to effector/memory migratory cells. While
CD40-activated CD4+ T cells were not required for eradicating treated-site tumors, they, plus CD8+ T cells, were crucial for removing distal tumors. Rechallenge/depletion experiments showed that the effector/memory phase
required the presence of previously CD40/IL-2-activated CD4+ and CD8+ T cells to prevent recurrence. These novel findings show that different T cell effector mechanisms can operate for the eradication
of local treated-site tumors versus untreated distal tumors and that signaling through CD40 generates a whole of body, effector/memory
CD4+ and CD8+ T cell response that is amplified and prolonged via IL-2. Thus, successful immunotherapy needs to generate collaborating
CD4+ and CD8+ T cells for a complete long-term protective cure. 相似文献
12.
Cao D van Vollenhoven R Klareskog L Trollmo C Malmström V 《Arthritis research & therapy》2004,6(4):R335-R346
CD25+CD4+ regulatory T cells participate in the regulation of immune responses. We recently demonstrated the presence of CD25brightCD4+ regulatory T cells with a capacity to control T cell proliferation in the joints of patients with rheumatoid arthritis. Here,
we investigate a possible accumulation of these regulatory T cells in the inflamed joint of different rheumatic diseases including
rheumatoid arthritis. The studies are also extended to analyze whether cytokine production can be suppressed by the regulatory
T cells. Synovial fluid and peripheral blood samples were obtained during relapse from 36 patients with spondyloarthropathies,
21 adults with juvenile idiopathic arthritis and 135 patients with rheumatoid arthritis, and the frequency of CD25brightCD4+ T cells was determined. Of 192 patients, 182 demonstrated a higher frequency of CD25brightCD4+ T cells in synovial fluid than in peripheral blood. In comparison with healthy subjects, the patients had significantly fewer
CD25brightCD4+ T cells in peripheral blood. For functional studies, synovial fluid cells from eight patients were sorted by flow cytometry,
and the suppressive capacity of the CD25brightCD4+ T cells was determined in in vitro cocultures. The CD25brightCD4+ T cells suppressed the production of both type 1 and 2 cytokines including interleukin-17, as well as proliferation, independently
of diagnosis. Thus, irrespective of the inflammatory joint disease investigated, CD25brightCD4+ T cells were reduced in peripheral blood and enriched in the joint, suggesting an active recruitment of regulatory T cells
to the affected joint. Their capacity to suppress both proliferation and cytokine secretion might contribute to a dampening
of local inflammatory processes. 相似文献
13.
Haibo Xue Weiwei Wang Zhongyan Shan Yuanbin Li Yushu Li Xiaochun Teng Yun Gao Chenling Fan Weiping Teng 《Biological trace element research》2011,143(1):292-301
Iodine is an essential trace element for thyroid hormone synthesis and metabolism, either low or high intake may lead to thyroid
disease, but the pathogenetic mechanisms by which iodine interacts with the thyroid autoimmune are poorly understood. We investigated
the dynamic changes of CD4+CD25+ regulatory T cells in NOD.H-2h4 mice with iodine-induced autoimmune thyroiditis (AIT), and explore potential immune mechanism of AIT induced by iodine. NOD.H-2h4 mice were randomly divided into two groups, and received plain water or water containing 0.005% sodium iodide. Eight weeks
after iodine provision, the incidences of thyroiditis, relative weights of thyroids, and serum thyroglobulin antibody titers
in the iodine-supplied groups were significantly increased compared to the control groups (p < 0.05). The AIT mice had fewer CD4+CD25+Foxp3+ T cells and reduced Foxp3 mRNA expression in splenocytes compared with the controls (p < 0.01), and maintained relatively low levels during the development of thyroiditis. The changes described above aggravated
gradually with the extension of iodine treatment. These data suggest that CD4+CD25+ regulatory T cells may be involved in the pathogenesis and development of AIT induced by iodine. 相似文献
14.
Wendy Ingram Shahram Kordasti Lucas Chan Linda D. Barber Gee J. Tye Nicola Hardwick Ghulam J. Mufti Farzin Farzaneh 《Cancer immunology, immunotherapy : CII》2009,58(10):1679-1690
Immunotherapeutic strategies are increasingly being explored as a method of enhancing anti-tumour immune responses in patients
with acute myeloid leukaemia (AML). Regulatory CD4+ T cells (Tregs) suppress effector T and natural killer (NK) cells and therefore pose a potential challenge to the efficacy
of immunotherapy. AML cells transduced with a lentivirus expressing CD80 (B7.1) and IL2 (LV-CD80/IL2) are capable of stimulating
T and NK cell cytotoxicity in vitro. This study examines the effect of CD80/IL2 modified AML cells on Treg number and function.
We report a significant increase in the number of CD8+ T cells (P = 0.046) CD3−CD56+ NK cells (P = 0.028) and CD3+CD4+CD25highFoxp3+ Tregs (P = 0.043) following stimulation for 7 days with allogeneic LV-CD80/IL2 AMLs. In contrast, autologous LV-CD80/IL2 AML cell
cultures provide a weaker stimulation with a lower number of CD8+ T cells (P = 0.011) and no change in NK cell or Treg numbers. However, an increase in cytotoxic CD8+ T cells and NK cells are detected following both allogeneic and autologous LV-CD80/IL2 stimulation as demonstrated by an
increase in IFN-γ and CD107a expression. Despite the presence of increased numbers of Tregs with suppressive activity in a
subset of cultures, increased lysis of unmodified AMLs was still achieved following allogeneic (day 0, 2.2%; day 7, 20.4%)
and more importantly, autologous LV-CD80/IL2 culture in which AML patients had recently received intensive chemotherapy (day
0, 0%; day 7, 16%). Vaccination with LV-CD80/IL2 therefore provides a potential strategy to enhance anti-leukaemia immune
responses without a concomitant stimulation of Treg-mediated inhibition of cytotoxic immunological responses. 相似文献
15.
Three mouse killer immunoglobulin-like receptors (KIRs), namely, KIR3DL1, KIRL1, and KIRL2, have recently been identified
in C56BL/6 (B6) mice. However, only two Kir genes are found in the B6 mouse genome sequence data base. To clarify this discrepancy, we cloned Kir cDNAs from multiple strains of mice. Sequencing of the cDNA clones showed that the Kir3dl1 gene is found in C3H/HeJ and CBA/J but not in B6 mice. Analysis of the single nucleotide polymorphism data base suggested
that Kir3dl1 is the C3H/HeJ and CBA/J allele of Kirl1. We generated mAb to the recombinant KIRL1 protein to investigate its expression pattern. The anti-KIRL1 mAb bound to NK1.1+ T cells but only very weakly or at undetectable levels to other lymphocytes including natural killer (NK) cells and conventional
T cells. Among NK1.1+ T cells, conventional NK T cells stained with CD1d tetramer did not significantly bind anti-KIRL1 mAb, whereas CD1d-tetramer-negative
subset was KIRL1-positive. Furthermore, the expression of KIRL1 is readily detected on NK1.1+ T cells from β2-microglobulin-deficient B6 mice. Thus, KIRL1 is predominantly expressed on CD1d-independent NK1.1+ T cells. 相似文献
16.
Wölfl M Merker K Morbach H Van Gool SW Eyrich M Greenberg PD Schlegel PG 《Cancer immunology, immunotherapy : CII》2011,60(2):173-186
T cell-mediated immunotherapy against malignancies has been shown to be effective for certain types of cancer. However, ex vivo expansion of tumor-reactive T cells has been hindered by the low precursor frequency of such cells, often requiring multiple rounds of stimulation, resulting in full differentiation, loss of homing receptors and potential exhaustion of the expanded T cells. Here, we show that when using highly purified naïve CD8+ T cells, a single stimulation with peptide-pulsed, IFNγ/LPS-matured dendritic cells in combination with the sequential use of IL-21, IL-7 and IL-15 is sufficient for extensive expansion of antigen-specific T cells. Short-term expanded T cells were tumor-reactive, multifunctional and retained a central-memory-like phenotype (CD62L+, CCR7+, CD28+). The procedure is highly reproducible and robust as demonstrated for different healthy donors and for cancer patients. Such short-term tumor-antigen-primed, multifunctional T cells may therefore serve as a platform to target different malignancies accessible to immunotherapy. 相似文献
17.
Hasegawa H Inoue A Muraoka M Yamanouchi J Miyazaki T Yasukawa M 《Arthritis research & therapy》2007,9(1):R15
Adoptive transfer of CD4+CD25+ regulatory T cells has been shown to have therapeutic effects in animal models of autoimmune diseases. Chemokines play an
important role in the development of autoimmune diseases in animal models and humans. The present study was performed to investigate
whether the progression of organ-specific autoimmune diseases could be reduced more markedly by accumulating chemokine receptor-expressing
CD4+CD25+ regulatory T cells efficiently in target organs in MRL/MpJ-lpr/lpr (MRL/lpr) mice. CD4+CD25+Foxp3+ T cells (Treg cells) and CD4+CD25+Foxp3+ CCR2-transfected T cells (CCR2-Treg cells) were transferred via retro-orbital injection into 12-week-old MRL/lpr mice at
the early stage of pneumonitis and sialadenitis, and the pathological changes were evaluated. Expression of monocyte chemoattractant
protein-1 (MCP-1)/CCL2 was observed in the lung and submandibular gland of the mice and increased age-dependently. The level
of CCR2 expression and MCP-1 chemotactic activity of CCR2-Treg cells were much higher than those of Treg cells. MRL/lpr mice
to which CCR2-Treg cells had been transferred showed significantly reduced progression of pneumonitis and sialadenitis in
comparison with MRL/lpr mice that had received Treg cells. This was due to more pronounced migration of CCR2-Treg cells and
their localization for a longer time in MCP-1-expressing lung and submandibular gland, resulting in stronger suppressive activity.
We prepared chemokine receptor-expressing Treg cells and demonstrated their ability to ameliorate disease progression by accumulating
in target organs. This method may provide a new therapeutic approach for organ-specific autoimmune diseases in which the target
antigens remain undefined. 相似文献
18.
Kazue Kogina Hirofumi Shoda Yumi Yamaguchi Nelson H. Tsuno Koki Takahashi Keishi Fujio Kazuhiko Yamamoto 《Molecules and cells》2009,28(2):125-130
Tacrolimus is a widely used T cell targeted immunosuppressive drug, known as a calcineurin inhibitor. However, the exact pharmacological
effects of tacrolimus on CD4+ T cells have yet to be elucidated. This study investigated the effects of tacrolimus on CD4+ T cell subsets. Mouse or human CD4+ T cells were cultured with immobilized anti-CD3/CD28 antibodies in the presence of tacrolimus. The cell division of CD4+ T cells was analyzed using a flow cytometer according to the expression of Foxp3. The gene expression patterns of tacrolimus-exposed
T cells were examined by quantitative PCR. In the case of conventional CD4+ T cells (Tconv cells), tacrolimus inhibited T cell receptor stimulation-induced cell division. In contrast, the cell division
of regulatory CD4+ T cells (Treg cells) was even promoted in the presence of tacrolimus, especially in humans. Tacrolimus did not promote conversion
of Tconv to Treg cells in mice. Furthermore, tacrolimus modified the expression levels of Foxp3-regulated T cell receptor
signal related-genes, PTPN22 and Itk, in human Treg cells. Immunosuppressive effect of tacrolimus may be attributed to the
relatively enhanced proliferation of Treg cells in association with altered gene expression levels of TCR signaling molecules. 相似文献
19.
Elkord E Burt DJ Drijfhout JW Hawkins RE Stern PL 《Cancer immunology, immunotherapy : CII》2008,57(6):833-847
Background The human 5T4 (h5T4) oncofoetal antigen is expressed by a wide variety of human carcinomas including colorectal, ovarian,
gastric and renal, but rarely on normal tissues. Its restricted expression on tumour tissues as well as its association with
tumour progression and bad prognosis has driven the development of a MVA-based vaccine (TroVax) which has been tested in several
early phase clinical trials and these studies have led to the start of a phase III trial in renal cell carcinoma patients.
We have recently shown that CD8+ T cells recognizing h5T4 can be generated in the absence of CD4+ T cells from peripheral blood lymphocytes of human healthy individuals.
Results We report the existence and expansion of human CD4+ T cells against h5T4 by stimulation with autologous monocyte-derived dendritic cells infected with a replication defective
adenovirus encoding the h5T4 cDNA (Ad-h5T4). The h5T4-specific T-cell responses in normal individuals are enhanced by initial
depletion of CD25+ cells (putative T regulatory cells) prior to the in vitro stimulation. We have identified a novel h5T4-derived 15-mer peptide
recognized by CD4+ T cells in HLA-DR4 positive healthy individuals. Interestingly, CD4+ T cells spontaneously recognizing a different 5T4 epitope restricted by HLA-DR were identified in tumour-infiltrating lymphocytes
isolated from a regressing renal cell carcinoma lung metastasis.
Conclusion Our data show that CD4+ T cells recognizing h5T4 can be expanded and detected in healthy individuals and a renal cell carcinoma patient. Such h5T4-specific
CD4+ T cells boosted or induced by vaccination could act to modulate both cell or antibody mediated anti-tumour responses.
This work was supported by Cancer Research UK. 相似文献
20.
Boot EP Koning GA Storm G Wagenaar-Hilbers JP van Eden W Everse LA Wauben MH 《Arthritis research & therapy》2005,7(3):R604-R615
T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid
arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60,
indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for
immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system.
Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority
of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not
internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized
cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis.
Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate
disease development. 相似文献