Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
J Exp Med ; 188(3): 609-14, 1998 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-9687538

RESUMO

CC chemokines produced by CD8(+) T cells are known to act as HIV-suppressive factors. We studied the possible role of these chemokines in HIV-1-specific killing of target cells. We found that the activity of cytotoxic T lymphocytes (CTLs) in CTL lines or freshly isolated peripheral blood mononuclear cells from HIV-1-infected individuals is markedly enhanced by RANTES (regulated on activation, normal T cell expressed and secreted) and virtually abolished by an antibody neutralizing RANTES or the RANTES receptor antagonist RANTES(9-68). Lysis was mediated by CD8(+) major histocompatibility complex class I-restricted T cells and was obtained with target cells expressing epitopes of the HIV-1LAI proteins Gag, Pol, Env, and Nef. The cytolytic activity observed in the presence or absence of added RANTES could be abolished by pretreatment of the CTLs with pertussis toxin, indicating that the effect is mediated by a G protein-coupled receptor. The chemokines monocyte chemotactic protein (MCP)-3, MCP-4, and eotaxin acted like RANTES, whereas macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MCP-1, and stromal cell-derived factor 1 were inactive, suggesting a role for the eotaxin receptor, CCR3, and ruling out the involvement of CCR1, CCR2, CCR5, and CXCR4. CTL activity was abrogated by an antibody that blocks CCR3, further indicating that specific lysis is triggered via this chemokine receptor. These observations reveal a novel mechanism for the induction of HIV-1-specific cytotoxicity that depends on RANTES acting via CCR3.


Assuntos
Quimiocina CCL5/imunologia , Citotoxicidade Imunológica , Infecções por HIV/imunologia , HIV-1/imunologia , Receptores de Quimiocinas/imunologia , Linhagem Celular , Quimiocina CCL5/farmacologia , Humanos , Receptores CCR3
2.
J Clin Invest ; 89(1): 53-60, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1370302

RESUMO

Cytotoxic T lymphocytes (CTL) specific for human immunodeficiency virus (HIV) proteins have been analyzed in lymphoid organs from seropositive patients. Indeed, an active HIV replication coexists with a major CD8+ lymphocytic infiltration in these organs. We have shown in a previous report that HIV-seropositive patients lungs were infiltrated by HIV specific CD8+ lymphocytes. In the present report, we show that HIV-specific CTL responses can also be detected in lymph nodes and spleens, and were mainly directed against the ENV, GAG, and NEF HIV-1 proteins. The primary NEF-specific CTL responses were further characterized by epitope mapping. Determination of epitope-specific CTL frequencies were performed by limiting dilution analysis. Our results indicated that, in addition to the central region of NEF (AA66-148), a new immunodominant region is recognized by CTL. This region corresponds to the carboxyl-terminal domain of NEF (amino acids 182-206). AA182-206 is recognized in association with at least two common human histocompatibility leukocyte antigen (HLA) molecules (HLA-A1 and B8), with clonal frequencies of one CTL per 10(-5) to 10(-6) splenic lymphocytes. Our data indicate that lymphoid organs may represent a major reservoir for in vivo activated HIV-specific CTL. Furthermore, the carboxyl-terminal domain of NEF was found to be conserved among several HIV strains. Therefore, our finding is of interest for further HIV vaccines development.


Assuntos
Produtos do Gene nef/imunologia , HIV-1/imunologia , Tecido Linfoide/imunologia , Oligopeptídeos/imunologia , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Epitopos/imunologia , Produtos do Gene env/imunologia , Produtos do Gene gag/imunologia , Antígenos HLA/imunologia , Humanos , Linfonodos/imunologia , Dados de Sequência Molecular , Oligopeptídeos/síntese química , Baço/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana
3.
J Clin Invest ; 101(11): 2506-16, 1998 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9616222

RESUMO

A massive infiltration of the skin by activated CD8+ T lymphocytes involving both the dermis and the epidermis has been found in HIV-1-infected patients presenting with a chronic skin rash. We characterized the T cell receptor (TCR) BV-BJ junctional diversity of the skin-infiltrating lymphocytes (SILs) in four patients. The SILs expressed a limited set of TCRBV gene segments. Complementarity determining region 3 length analysis further emphasized their oligoclonality, suggesting that antigen stimulation might be responsible for the cutaneous T cell expansion. Furthermore, independent skin biopsies obtained from the same individual were shown to harbor distinct T cell repertoires, possibly reflecting the spatial heterogeneity of the antigenic stimuli. The CD8+ cytotoxic T lymphocyte (CTL) lines isolated from the skin rash in one patient exhibited a specific, class I MHC-restricted cytotoxic activity against HIV-1 Gag- and Pol-expressing target cells, whereas CTL lines derived from the skin lesions of a second patient were shown to be predominantly Env-specific. Taken together, these data demonstrate the infiltration of HIV-specific CTLs in the skin of HIV-infected patients, and suggest that in addition to their known role in controlling the retroviral infection, these CTLs may also be involved in the pathogenesis of cutaneous inflammatory disorders occurring during the course of HIV infection.


Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , HIV-1/imunologia , Pseudolinfoma/imunologia , Dermatopatias/imunologia , Linfócitos T Citotóxicos/fisiologia , Adulto , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/genética
4.
Curr Opin Immunol ; 8(4): 546-53, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8794018

RESUMO

Exceptionally potent cytotoxic T lymphocyte responses are generated after HIV invasion and probably control the primary infection as well as the asymptomatic phase of HIV infection. The chronic phase appears as a quasi-equilibrium between waves of new HIV variants and variant-specific CTLs, thus sustaining continuous CTL activation which eventually fails to eradicate HIV disease progression and the reascension of viral replication. Meanwhile, both the host and the virus develop various strategies either to stop or to evade this potentially deleterious permanent CTL activity. The transient effectiveness of CTLs opens perspectives for understanding disease progression generally as well as for immune therapeutic strategies.


Assuntos
Evolução Molecular , HIV/imunologia , Linfócitos T Citotóxicos/classificação , Linfócitos T Citotóxicos/imunologia , Portador Sadio/imunologia , Humanos
5.
AIDS ; 5(12): 1453-61, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1726040

RESUMO

A new Amphotericin B derivative, MS-8209, which retains high antifungal activity with greatly reduced toxicity and improved solubility, has been developed. We investigated the antiviral properties of MS-8209 in Jurkat and CEM T-cell lines and in peripheral blood mononuclear cells infected in vitro with HIV-1BRU. Our results demonstrate, by determination of reverse transcriptase activity and p24 antigen level titration in cell culture supernatants, that MS-8209 inhibits HIV-1 replication in all cell types at concentrations without cytotoxicity. MS-8209 also prevents membrane expression of the HIV-1 large envelope glycoprotein gp120 and the decrease in CD4 level at the surface of infected cells. HIV-1-infected Jurkat cells exhibit a severe signalling defect at CD3 stimulation. Treatment with MS-8209 restores normal responsiveness at CD3 as assessed by measurement of inositol triphosphate accumulation and calcium flux. Finally, our results indicate that MS-8209 inhibits HIV-1BRU replication without preventing virus binding and penetration into target cells.


Assuntos
Anfotericina B/análogos & derivados , Antivirais/farmacologia , Linfócitos T CD4-Positivos/microbiologia , HIV-1/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Anfotericina B/farmacologia , Antígenos de Diferenciação de Linfócitos T/fisiologia , Complexo CD3 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Proteína do Núcleo p24 do HIV/análise , Proteína gp120 do Envelope de HIV/metabolismo , Transcriptase Reversa do HIV , Humanos , Cinética , Microscopia de Fluorescência , DNA Polimerase Dirigida por RNA/metabolismo , Receptores de Antígenos de Linfócitos T/fisiologia , Fosfolipases Tipo C/metabolismo
6.
Hum Gene Ther ; 10(11): 1803-10, 1999 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-10446920

RESUMO

CTL lines directed against HIV-1 antigens were generated from infected individuals and were transduced by the HMB-K(b)HuIFNbeta vector, resulting in low, constitutive expression of interferon beta (IFN-beta). The IFN-beta-transduced cells showed markedly increased HIV-1-specific, MHC class I-restricted CTL activity against HIV-1-LAI Gag, Pol, or Env antigens. This effect of IFN-beta was correlated with an overexpression of RANTES and completely abrogated by RANTES-blocking antibody. The present results provide the first evidence that IFN-beta transduction of CTL lines enhances HIV-specific cytotoxic activities through an upregulation of RANTES production. The efficient elimination of HIV-infected cells by IFN-beta-transduced CTL lines makes this gene therapy approach an attractive treatment for AIDS.


Assuntos
Quimiocina CCL5/metabolismo , Terapia Genética , Infecções por HIV/terapia , HIV-1/imunologia , Interferon beta/genética , Linfócitos T Citotóxicos/imunologia , Citotoxicidade Imunológica/genética , Citometria de Fluxo , Vetores Genéticos , Infecções por HIV/imunologia , Humanos , Interferon beta/metabolismo , Receptores de Quimiocinas/metabolismo , Retroviridae/genética , Linfócitos T Citotóxicos/virologia , Transdução Genética
7.
Immunol Lett ; 57(1-3): 63-8, 1997 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9232427

RESUMO

Infection with the human immunodeficiency virus (HIV) results in a disease characterized by a rapid viral replication, immunodeficiency and chronic immune activation. The vigorous polyspecific cytotoxic T-cell (CTL) response directed against multiple HIV epitopes reduces HIV-infected cell numbers, although unable to eradicate the virus. The plasticity of the specific CTL repertoire ensures adaptation to the high rate of viral variation that can be found in CTL epitopes of several HIV-1 proteins. However, viral persistence occurs despite continuous CTL recognition and although functional importance of conserved sites in the different HIV proteins may impose constraints to viral variation. In the reverse transcriptase (RT) which is a major target for antiretroviral therapy, the impact of the continuous pressure of drug therapy is more obvious than that of the CTLs. Shifts in immunodominant RT regions seem to allow the maintenance of the HIV-1 RT CTL recognition with disease progression and antiretroviral therapy. In respect to new highly active drug combinations, understanding the capacity of virus-specific CTLs to control residual viral variants seems very important and may allow development of efficient immunotherapies to prevent drug-induced viral resistance.


Assuntos
Variação Genética , HIV/genética , HIV/imunologia , Linfócitos T Citotóxicos/imunologia , Adaptação Fisiológica , Fármacos Anti-HIV , Progressão da Doença , Epitopos/imunologia , Transcriptase Reversa do HIV/imunologia , Humanos
8.
Anticancer Res ; 7(4B): 861-7, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3674775

RESUMO

Many Experimental and human tumor cell lines have been previously described as being dependent upon exogenous methionine for their in vitro proliferation. The rationale of the experiments described herein was to decrease the in vivo growth of malignant tumors by reducing the exogenous methionine available in diets fed to Wistar AG rats bearing the highly metastatic rhabdomyosarcoma, RMS-J1. The methionine content in the diet was reduced either by replacing casein (diet 1) with soybean protein (diet 4), or by lowering the amount of soybean protein in the diet (from 23 g/100 g to 12 g/100g) (diet 5), or by using a crystalline amino acid-defined mixture as the source of protein (diet 7). In the latter diet homocysteine replaced methionine and allowed the survival of the animals. Diet 4 significantly reduced the mean number of lung metastases without affecting the primary tumor growth. Treatment of RMS-J1 bearing rats with diet 5 led to the decrease of pulmonary invasion (78 and 21 median lung metastases, respectively, in control and treated groups). This diminished metastatic dissemination resulted from the reduced methionine consumption: the lowered casein content in diet 3 (10 g/100 g) as compared to diet 1 (23 g) did not alter primary tumor growth or the amplitude of lung invasion. Moreover, the addition of methionine to diet 5 prevented the diminution of the median number of lung metastases. Replacement of methionine with homocysteine in the crystalline amino acid-defined mixture (diet 7) fed to RMS-J1 bearing rats led to a limited retardation of primary tumor growth (less than 10%) and to a significant decrease in pulmonary invasion: the median number of pulmonary metastases was 28 and 9 for control and treated rats respectively.


Assuntos
Neoplasias Pulmonares/secundário , Metionina/deficiência , Rabdomiossarcoma/patologia , Animais , Dieta , Homocisteína/metabolismo , Metástase Neoplásica , Neoplasias Experimentais/dietoterapia , Neoplasias Experimentais/patologia , Ratos , Rabdomiossarcoma/dietoterapia
9.
Adv Exp Med Biol ; 374: 173-82, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7572391

RESUMO

Human immunodeficiency virus (HIV) replication and T cell proliferation was investigated in situ by a PCR based analysis of individual microdissected splenic white pulps. Founder effects, revealed by an exquisite compartmentalization of HIV genotypes and T cells, indicated the recruitment of latently infected CD4+ T cells through highly localized antigen presentation, rather than the infection of CD4+ T lymphoblasts by blood borne virus or immune complexes. HIV infected white pulps could be infiltrated by HIV specific cytotoxic T lymphocytes, so implicating them in CD4+ T cell destruction in vivo. Together these data describe an iterative and deleterious mechanism of antigen driven T cell recruitment and activation, HIV replication and spread, with consequent destruction of the newly infected cells.


Assuntos
Anticorpos Anti-HIV , HIV/fisiologia , Baço/patologia , Linfócitos T Citotóxicos , Replicação Viral , Sequência de Aminoácidos , Especificidade de Anticorpos , Células Clonais , Dissecação , Genótipo , HIV/genética , Humanos , Micromanipulação , Dados de Sequência Molecular
10.
J Immunol ; 163(3): 1105-9, 1999 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10415001

RESUMO

Based on the previous observation that RANTES mediates the cytotoxic activity of human HIV-specific CD8+ T cells via the chemokine receptor CCR3, we studied the effect of this chemokine on different effector CD8+ cytolytic cells requiring Fas/Fas ligand (FasL) or perforin-dependent pathway. In CTLs derived from PBMCs of HIV-infected patients, both the spontaneous and the RANTES-induced cytotoxicity were inhibited by anti-FasL neutralizing Abs. In contrast, allogeneic CTLs or NK cells killing through perforin were not affected by RANTES and anti-FasL Ab. Accordingly, RANTES enhanced the expression of FasL in a concentration- and time-dependent manner in HIV-specific CTLs, whereas anti-RANTES Ab decreased markedly FasL expression. Finally, cell surface expression of FasL protein in HIV-specific CTLs was also up-regulated by eotaxin, a selective ligand for CCR3. Our observations show that the action of RANTES via CCR3 is necessary to regulate FasL expression on HIV-specific CD8+ T cells that kill through the Fas/FasL pathway.


Assuntos
Quimiocina CCL5/fisiologia , Citotoxicidade Imunológica/imunologia , HIV-1/imunologia , Glicoproteínas de Membrana/biossíntese , Linfócitos T Citotóxicos/imunologia , Receptor fas/metabolismo , Adjuvantes Imunológicos/fisiologia , Linhagem Celular , Epitopos de Linfócito T/imunologia , Proteína Ligante Fas , Humanos , Ligantes , Glicoproteínas de Membrana/metabolismo , RNA Mensageiro/biossíntese , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Citotóxicos/metabolismo , Transcrição Gênica/imunologia , Receptor fas/genética
11.
Res Virol ; 142(2-3): 113-8, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1832781

RESUMO

To analyse the evolution of alveolar-lymphocyte-mediated cytotoxic activity directed against autologous alveolar macrophages (AM), cytotoxic assays against various HIV+ target cells were performed in a cohort of 75 patients with HIV-associated lymphoid interstitial pneumonitis (LIP) studied at distinct stages of HIV infection. Our data confirm that alveolar HIV-specific cytotoxic T lymphocytes (CTL) against AM were detectable before AIDS in patients with CD8+ LIP. Mild CD8+ lymphocytic alveolitis occurs silently in 62% of stage II and III patients with no respiratory symptoms. In these cases, the lack of spontaneous alveolar-lymphocyte-mediated cytotoxic activity against autologous AM may contrast with the detection of primary alveolar CTL specific for HIV proteins such as nef. In AIDS patients, the alveolar CTL lytic efficiency against both AM- and HIV-antigen-expressing cells can be inhibited by a suppressor factor produced by alveolar CD8+ CD57+ cells. Therefore, spontaneous CTL lysis of AM may be (1) limited to a subgroup of patients with active LIP and (2) controlled by distinct mechanisms, including suppressor phenomenons, and HIV replication levels in AM.


Assuntos
Infecções por HIV/imunologia , HIV/imunologia , Macrófagos/microbiologia , Linfócitos T Citotóxicos/imunologia , Estudos de Coortes , Testes Imunológicos de Citotoxicidade , Regulação para Baixo , Infecções por HIV/complicações , Humanos , Macrófagos/imunologia , Alvéolos Pulmonares/citologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/imunologia , Linfócitos T Reguladores/imunologia , Replicação Viral
12.
J Immunol ; 154(8): 4174-86, 1995 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-7535824

RESUMO

In a previous analysis of HIV-1-specific CTLs in lymphoid organs from HIV-seropositive patients, we reported high frequencies of in vivo differentiated CTLs directed against two immunodominant regions in the central and in the C-terminal part of the HIV-1 Nef protein. The present study analyzes the epitopes recognized by CTLs in the carboxyl terminus of Nef (amino acids 182-205). In addition to several epitopes that are recognized in association with different HLA molecules (A1, A2, A25(10), B35, B52), we defined an optimal nonapeptide (190-198). This nonapeptide was recognized by CTLs down to nanomolar concentrations in the context of at least two HLA molecules, HLA-B52 and HLA-A2, including three HLA-A2 subtypes: HLA-A2.1, -A2.2, and -A2.4. We also determined the relative frequencies of effector CTLs directed against peptide 190-198 to be as high as 10(-4), as opposed to lower frequencies ranging between 5 x 10(-5) and 5 x 10(-6) observed for the other peptides recognized in the same region, thus confirming the optimal presentation of this nonapeptide in vivo. Molecular modeling of the interactions between HLA-A2.1 and Nef peptide 190-198 suggests the formation of a stable complex and allowed us to study sequence motifs that are important for the binding of the HIV-1 peptide in the pockets of the HLA-A2.1 molecule.


Assuntos
Produtos do Gene nef/imunologia , Antígenos HIV/imunologia , Soropositividade para HIV/imunologia , HIV-1/imunologia , Antígeno HLA-A2/imunologia , Antígenos HLA-B/imunologia , Linfócitos T Citotóxicos/imunologia , Sequência de Bases , Simulação por Computador , Citotoxicidade Imunológica , Mapeamento de Epitopos , Epitopos/química , Antígeno HLA-B52 , Humanos , Imunidade Celular , Técnicas In Vitro , Linfonodos/imunologia , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Baço/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana
13.
Eur J Immunol ; 24(11): 2882-8, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7525310

RESUMO

An inhibitor of the cytotoxic functions (ICF) mediated by human immunodeficiency virus (HIV)- or HLA-specific cytotoxic T lymphocytes, natural killer and lymphokine-activated killer (LAK) cells is secreted by CD8+CD57+ T lymphocytes, a subset expanded during infection with HIV and after bone marrow transplantation. We previously showed an apparent molecular mass of 20-30 kDa for this soluble glycosylated concanavalin A-binding inhibitor which is distinct from known cytokines. Here, we report a characterization of the mechanism of action of this CD8+CD57+ ICF. We show that the ICF-induced inhibition of LAK cell cytolytic activity is transient, with a spontaneous recovery of cytolytic potential after 18 h. When testing interactions of ICF with a large set of cytokines we found that the ICF-mediated inhibition of cytotoxic functions is antagonized by two cytokines: recombinant interleukin (rIL)-4 and recombinant interferon (rIFN)-gamma. Finally, we show that ICF acts at the level of cytolytic effector cells, where it induces a significant increase of cyclic AMP (cAMP) level. In contrast, no modification of either cell surface antigen expression or of target/effector cell conjugate formation could be evidenced. Addition of rIL-4 and rIFN-gamma reverses such an increase of cAMP levels and in parallel restores the cytolytic activity. Altogether, these data demonstrate that the glycoprotein ICF produced by CD8+CD57+ cells (1) inhibits cell-mediated cytotoxicity by sensitizing cytolytic effector cells to the cAMP pathway, and (2) is part of a cytokine network controlling cell-mediated cytotoxic functions.


Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Antígenos CD8/análise , Citotoxicidade Imunológica/efeitos dos fármacos , Glicoproteínas/farmacologia , Tolerância Imunológica , Subpopulações de Linfócitos T/fisiologia , Transplante de Medula Óssea , Antígenos CD57 , AMP Cíclico/biossíntese , Humanos , Interferon gama/farmacologia , Interleucina-4/farmacologia , Proteínas Recombinantes/farmacologia , Subpopulações de Linfócitos T/imunologia
14.
Cell ; 78(3): 373-87, 1994 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-7914835

RESUMO

Human immunodeficiency virus (HIV) replication and T cell proliferation were investigated in situ by a PCR-based analysis of individual microdissected splenic white pulps. Founder effects, revealed by an exquisite compartmentalization of HIV genotypes and T cells, indicated the recruitment of latently infected CD4+ T cells through highly localized antigen presentation rather than the infection of CD4+ T lymphoblasts by blood-borne virus or immune complexes. HIV-infected white pulps could be infiltrated by HIV-specific cytotoxic T lymphocytes, thereby implicating them in CD4+ T cell destruction in vivo. Together these data describe an iterative and deleterious mechanism of antigen-driven T cell recruitment and activation, as well as HIV replication and spread, with consequent destruction of the newly infected cells.


Assuntos
Soropositividade para HIV/imunologia , HIV/genética , Baço/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Apresentação de Antígeno , Sequência de Bases , Linfócitos T CD4-Positivos/imunologia , Movimento Celular , HIV/crescimento & desenvolvimento , Humanos , Ativação Linfocitária , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Provírus/genética , Provírus/crescimento & desenvolvimento , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Homologia de Sequência de Aminoácidos , Baço/citologia
15.
J Immunol ; 161(4): 2060-9, 1998 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-9712080

RESUMO

SCID-hu mouse models are of interest in the pathologic investigation of HIV infection, but obtaining a T cell response in SCID-hu-PBL mice is still controversial. We have developed a SCID model by engrafting human skin and autologous PBLs from HIV-seronegative individuals. The study describes the ability of this human-mouse chimera to generate in vivo a primary T lymphocyte response against HIV Ag. The injection of human autologous PBLs was performed 4 to 5 wk after the skin engraftment. Two weeks after injection of PBLs, chimeric mice were immunized with recombinant canary pox virus expressing HIV-1 LAIgp160 (vCP-LAIgp160) and supplemented or not with rIL-2. Intradermal vCP-LAIgp160 injection induced an intradermal perivascular human lymphocytic infiltrate and an epidermic network of CD1a+, CD80+, and CD86+ cells. We derived CD4+ T cell lines (STLs) from the human skin graft of immunized mice, showing that STLs mediated an MHC class II-restricted cytolytic activity directed against HIV-LAIgp160 Ags. Cytokine gene expression in both human skin cells and in STLs showed a predominance of IL-2, IFN-gamma, and IL-12 transcripts. Finally, the T cell repertoire analysis using the immunoscope technique showed a very limited CDR3 length polymorphism in the skin infiltrating lymphocytes suggesting an Ag-specific repertoire. The ability to induce a primary Th1 cell response in vivo affords a useful preclinical model for testing vaccine strategies.


Assuntos
Transferência Adotiva/métodos , Proteína gp160 do Envelope de HIV/imunologia , Transfusão de Linfócitos , Transplante de Pele/imunologia , Células Th1/transplante , Animais , Antígenos CD1/análise , Antígenos Virais/imunologia , Avipoxvirus/genética , Avipoxvirus/imunologia , Linhagem Celular , Movimento Celular/imunologia , Quimera/imunologia , Citocinas/biossíntese , Citocinas/genética , Epitopos de Linfócito T/imunologia , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Proteína gp160 do Envelope de HIV/genética , HIV-1/genética , HIV-1/imunologia , Humanos , Injeções Intradérmicas , Células de Langerhans/imunologia , Leucócitos/patologia , Camundongos , Camundongos SCID , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Pele/imunologia , Pele/metabolismo , Pele/patologia , Transplante de Pele/métodos , Transplante de Pele/patologia , Linfócitos T/citologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Células Th1/imunologia , Células Th1/metabolismo
16.
Eur J Immunol ; 21(3): 737-41, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1707006

RESUMO

CD8+CD57+ T cells, expanded in peripheral blood lymphocytes of AIDS patients, inhibit the effector phase of HLA-specific cytotoxic T lymphocytes, natural killer and lymphocyte-activated killer cells in a 4-h chromium-release assay. This inhibitory activity present in supernatants of purified sorted CD8+CD57+ cells is mediated by a non-antigen-specific inhibitory factor which is distinct from prostaglandin E2, T cell growth factor (TGF)-beta, latent-TGF-beta, tumor necrosis factor (TNF)-alpha and TNF-beta. Partial biochemical characterization demonstrates that the CD8+CD57+ inhibitory activity (a) is heat, trypsin and acid resistant, (b) binds to concanavalin A columns, indicating its glycosylation state and (c) is mediated by a 20-30-kDa soluble molecule.


Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Citotoxicidade Imunológica , Fatores Supressores Imunológicos/fisiologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos de Diferenciação de Linfócitos T/análise , Antígenos CD57 , Antígenos CD8 , Humanos , Imunidade Celular , Técnicas In Vitro , Lectinas/metabolismo , Peso Molecular , Solubilidade , Fatores Supressores Imunológicos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA