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1.
Immunology ; 137(4): 305-16, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23167249

RESUMO

In this study, we investigated the effects of administration of interleukin-2 (IL-2)/JES6-1 (anti-IL-2 monoclonal antibody) immune complexes on the expansion and activation of regulatory T (Treg) cells, the down-regulation of T helper type 17 (Th17) cells, and the control of the severity of collagen-induced arthritis (CIA). Wild-type and CIA-induced wild-type mice were injected intraperitoneally (i.p.) with IL-2 or IL-2/JES6-1 complex three times at 2-day intervals. Treg cell surface markers were analysed by flow cytometry. After injecting IL-2 or IL-2/JES6-1, the time kinetics of IL-2 signalling molecules was examined by FACS and Western blotting. Concentrations of IL-17 and IL-10 were measured by ELISA. Injection of IL-2/JES6-1 increased the proportion of Foxp3+ Treg cells among splenic CD4+ T cells, which reached the highest level on day 4 after injection. Up-regulation of CTLA4, GITR and glycoprotein-A repetitions predominant (GARP) was observed. Activation of p-signal transducer and activator of transcription 5 (STAT5) was apparent within 3 hr after injection of IL-2/JES6-1 complexes. Expression of IL-2 signalling molecules, including p-AKT and p-p38/mitogen-activated protein kinase, was also higher in splenocytes treated with IL-2/JES6-1 complexes. Injection of IL-2/JES6-1 complexes suppressed the induction of CIA and the production of IL-17 and inflammatory responses while increasing the level of IL-10 in the spleen. The expansion of Treg cells (via STAT5) and the concomitant increase in IL-2 signalling pathways by IL-2/JES6-1 complexes suggests their potential use as a novel therapeutic agent for the treatment of autoimmune arthritis.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Complexo Antígeno-Anticorpo/uso terapêutico , Artrite Experimental/tratamento farmacológico , Interleucina-2/imunologia , Fator de Transcrição STAT5/fisiologia , Transdução de Sinais/fisiologia , Animais , Anticorpos Monoclonais/farmacologia , Complexo Antígeno-Anticorpo/imunologia , Complexo Antígeno-Anticorpo/farmacologia , Interleucina-2/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos DBA , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/fisiologia , Células Th17/fisiologia
2.
Immunol Cell Biol ; 90(7): 743-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21946662

RESUMO

Immune complexes combining IL-2 with particular anti-IL-2 antibodies can be used to selectively expand regulatory T cells or memory T cells. Combining IL-2 with anti-IL-2 (Clone S4B6) greatly enhances the biological potency of IL-2 in vivo leading to selective expansion of CD8 memory T cells and NK cells compared with regulatory T cells. Here we show that in vivo administration of IL-2/anti-IL-2 mAb (IL-2/mAb) complexes induces 4-1BB expression on both adoptively transferred antigen-specific memory CD8 T cells as well as on endogenous memory phenotype cells. Remarkably, the accumulation of adoptively transferred memory CD8 T cells following in vivo IL-2/mAb-complex treatment was found to be dependent in part on the presence of 4-1BBL in the host. These effects were independent of IL-2-induced cell division, suggesting that 4-1BBL-induced survival signals contribute to IL-2/mAb-complex-induced T-cell accumulation in vivo.


Assuntos
Ligante 4-1BB/imunologia , Anticorpos Monoclonais/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Interleucina-2/farmacologia , Ligante 4-1BB/deficiência , Ligante 4-1BB/genética , Transferência Adotiva , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Citometria de Fluxo , Memória Imunológica/imunologia , Interleucina-2/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
3.
Hemodial Int ; 7(4): 320-5, 2003 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19379382

RESUMO

BACKGROUND: The major source of catheter-associated bacteremia is contamination of the catheter hub during connection-disconnection procedures. A new method of catheter locking has been developed wherein anticoagulant is injected first, followed by a 0.1-mL air bubble and 0.9 mL of bactericidal solution. The anticoagulant is then located at the catheter tip and the bactericidal solution is located at the catheter hub. The air bubble prevents mixing of the two solutions. The bactericidal solution was acidified concentrated saline (ACS). The 27% saline solution has a pH of 2.0. ACS was chosen because it is theoretically harmless if injected in the amount used to lock the catheter lumens. The goals of this pilot study were to determine whether the new method of catheter locking is easy to perform with available syringes and whether eventual injection of the experimental solution is well tolerated. METHODS: Ten patients were randomly assigned, either to heparin lock (5 patients, 62 treatments) or air-bubble method (5 patients, 56 treatments). In the control group, the catheters were locked with heparin, 5000 U/mL. In the experimental group, the catheters were locked with heparin, air bubble, and ACS. Altogether, the lumens were overfilled by 0.2 mL. RESULTS: Compared to the routine method, the experimental method required a 1- to 2-min-longer procedure time. There were no errors in proper sequence of injections into the lumina. There were no episodes of bacteremia related to hub contamination in either group. In the air-bubble group, there was one case of bacteremia associated with purulent drainage from the exit and the same organism in both cultures. In three instances in each group, the locking solution could not be aspirated and was injected without any subjective symptoms or objective signs. CONCLUSION: We conclude that the air-bubble method of locking central-vein catheters is easy to perform. In three instances of air-bubble and ACS injection, there were no adverse effects. A full-scale prospective randomized study is feasible and warranted.

4.
Mol Ther Methods Clin Dev ; 1: 14054, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26052522

RESUMO

The immunocompetence and clinical accessibility of dermal tissue offers an appropriate and attractive target for vaccination. We previously demonstrated that pDNA injection into the skin in combination with surface electroporation (SEP), results in rapid and robust expression of the encoded antigen in the epidermis. Here, we demonstrate that intradermally EP-enhanced pDNA vaccination results in the rapid induction of a host humoral immune response. In the dermally relevant guinea pig model, we used high-resolution laser scanning confocal microscopy to observe direct dendritic cell (DC) transfections in the epidermis, to determine the migration kinetics of these cells from the epidermal layer into the dermis, and to follow them sequentially to the immediate draining lymph nodes. Furthermore, we delineate the relationship between the migration of directly transfected epidermal DCs and the generation of the host immune response. In summary, these data indicate that direct presentation of antigen to the immune system by DCs through SEP-based in vivo transfection in the epidermis, is related to the generation of a humoral immune response.

5.
Methods Mol Biol ; 979: 81-106, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23397391

RESUMO

Under normal circumstances, the secondary lymphoid tissues contain a predictable number of T cells with a diverse T cell receptor (TCR) repertoire. Such a T cell pool must be of sufficient size to confer maximum protection of the host from infectious pathogens and cancer, but small enough not to overburden the host. The T cell pool is maintained by a combination of de novo T cell production by the thymus and by the long-term survival and gradual turnover of mature T cells in the periphery. The latter process, termed homeostatic proliferation, has been intensely investigated over the past 20 years, and a few techniques have been developed to facilitate these studies. In this chapter, we describe the experimental procedures that allow conspicuous visualization of homeostatic proliferation, which have been instrumental in facilitating recent advances in the study of T cell homeostasis.


Assuntos
Homeostase , Ativação Linfocitária , Linfócitos T/citologia , Linfócitos T/imunologia , Transferência Adotiva , Animais , Células da Medula Óssea/citologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Proliferação de Células , Feminino , Histocompatibilidade , Antígenos de Histocompatibilidade Classe I/imunologia , Interleucina-15/metabolismo , Interleucina-7/metabolismo , Linfonodos/citologia , Imãs/química , Camundongos , Microesferas , Baço/citologia , Linfócitos T/metabolismo
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