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1.
PLoS One ; 10(3): e0118654, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25781898

RESUMO

The ability of antigen-specific T cells to simultaneously produce multiple cytokines is thought to correlate with the functional capacity and efficacy of T cells. These 'polyfunctional' T cells have been associated with control of HIV. We aimed to assess the impact of co-infection with Mycobacterium tuberculosis (MTB) on HIV-specific CD8+ and CD4+ T cell function. We assessed T cell functionality in 34 South African adults by investigating the IFN-y, IL-2, TNF-α, IL-21 and IL-17 cytokine secretion capacity, using polychromatic flow cytometry, following HIV Gag-specific stimulation of peripheral blood mononuclear cells. We show that MTB is associated with lower HIV-specific T cell function in co-infected as compared to HIV mono-infected individuals. This decline in function was greatest in co-infection with active Tuberculosis (TB) compared to co-infection with latent MTB (LTBI), suggesting that mycobacterial load may contribute to this loss of function. The described impact of MTB on HIV-specific T cell function may be a mechanism for increased HIV disease progression in co-infected subjects as functionally impaired T cells may be less able to control HIV.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , HIV/imunologia , Mycobacterium tuberculosis/imunologia , Adulto , Coinfecção/imunologia , Feminino , Citometria de Fluxo , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Interferon gama/metabolismo , Interleucina-17/metabolismo , Interleucina-2/metabolismo , Interleucinas/metabolismo , Tuberculose Latente/complicações , Tuberculose Latente/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Tuberculose/complicações , Tuberculose/imunologia , Fator de Necrose Tumoral alfa/metabolismo
2.
AIDS ; 28(18): 2671-6, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25211438

RESUMO

OBJECTIVES: This study aimed to assess how Mycobacterium tuberculosis (MTB) coinfection alters the impact of interleukin-10 in chronic HIV infection. DESIGN: We assessed plasma cytokine levels (interleukin-10, interferon-γ, tumor necrosis factor-α, interleukin-2, interleukin-6 and interleukin-13) in 82 individuals presenting with HIV monoinfection, HIV-LTBI (latent MTB infection) coinfection or HIV-TB (active tuberculosis) coinfection. We also assessed the influence of MTB on the functional impact of interleukin-10 receptor alpha (interleukin-10Rα) blockade on HIV and MTB-specific CD4(+) T cells. METHODS: Plasma cytokine levels were measured by high sensitivity Luminex. We used an ex-vivo interleukin-10Rα blockade assay to assess if functional enhancement of HIV and MTB-specific CD4(+) T cells was possible following a 48-h stimulation with HIV gag or pooled ESAT-6 (6 kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein) peptides. Cell supernatant was collected 48 h after stimulation and the cytokine profile was measured by Luminex. RESULTS: Plasma interleukin-10 levels were elevated in HIV-TB as compared with HIV monoinfection (P < 0.05) and HIV-LTBI (P < 0.05). Plasma interleukin-10 levels correlated to HIV viral load in HIV monoinfection (P = 0.016) and HIV-LTBI (P = 0.042), but not HIV-TB. Ex-vivo blockade of interleukin-10Rα significantly enhanced MTB and HIV-specific CD4(+) T-cell function in HIV-LTBI individuals but not in HIV-TB individuals. CONCLUSION: Tuberculosis disrupts the correlation between interleukin-10 and markers of HIV disease progression. In addition, HIV-TB is associated with a more inflammatory cytokine milieu compared with HIV monoinfection. Interestingly, interleukin-10Rα blockade can enhance both HIV and MTB-specific T-cell function in HIV-LTBI, but not in HIV-TB coinfection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Interleucina-10/sangue , Mycobacterium tuberculosis/imunologia , Tuberculose/complicações , Tuberculose/imunologia , Humanos , Interleucina-10/imunologia
3.
PLoS One ; 8(12): e83474, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24391773

RESUMO

BACKGROUND: High expression of CD161 on CD8+ T cells is associated with a population of cells thought to play a role in mucosal immunity. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting. METHODS: A flow cytometric approach was used to assess the frequency and phenotype of CD161++CD8+ T cells. 80 individuals were recruited for cross-sectional analysis: controls (n = 18), latent MTB infection (LTBI) only (n = 16), pulmonary tuberculosis (TB) only (n = 8), HIV only (n = 13), HIV and LTBI co-infection (n = 15) and HIV and TB co-infection (n = 10). The impact of acute HIV infection was assessed in 5 individuals recruited within 3 weeks of infection. The frequency of CD161++CD8+ T cells was assessed prior to and during antiretroviral therapy (ART) in 14 HIV-positive patients. RESULTS: CD161++CD8+ T cells expressed high levels of the HIV co-receptor CCR5, the tissue-homing marker CCR6, and the Mucosal-Associated Invariant T (MAIT) cell TCR Vα7.2. Acute and chronic HIV were associated with lower frequencies of CD161++CD8+ T cells, which did not correlate with CD4 count or HIV viral load. ART was not associated with an increase in CD161++CD8+ T cell frequency. There was a trend towards lower levels of CD161++CD8+ T cells in HIV-negative individuals with active and latent TB. In those co-infected with HIV and TB, CD161++CD8+ T cells were found at low levels similar to those seen in HIV mono-infection. CONCLUSIONS: The frequencies and phenotype of CD161++CD8+ T cells in this South African cohort are comparable to those published in European and US cohorts. Low-levels of this population were associated with acute and chronic HIV infection. Lower levels of the tissue-trophic CD161++ CD8+ T cell population may contribute to weakened mucosal immune defense, making HIV-infected subjects more susceptible to pulmonary and gastrointestinal infections and detrimentally impacting on host defense against TB.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Imunidade nas Mucosas , Subfamília B de Receptores Semelhantes a Lectina de Células NK/metabolismo , Subpopulações de Linfócitos T/imunologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose Latente/complicações , Tuberculose Latente/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , África do Sul , Adulto Jovem
4.
PLoS One ; 7(6): e37920, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22685549

RESUMO

Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3-21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from -150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r=0.6527, p=0.0114; IP-10: r=0.6967, p=0.0056; IP-10+MIG: r=0.7055, p=0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting.


Assuntos
Infecções por HIV/imunologia , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Tuberculose/imunologia , Contagem de Linfócito CD4 , Quimiocina CXCL10/genética , Quimiocina CXCL9/genética , Coinfecção/diagnóstico , Coinfecção/imunologia , ELISPOT/métodos , HIV/imunologia , Infecções por HIV/diagnóstico , Humanos , Limite de Detecção , Estudos Prospectivos , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/metabolismo , Fatores de Tempo , Tuberculose/diagnóstico , Carga Viral
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