scholarly journals Low Levels of Perforin Expression in CD8+T Lymphocyte Granules in Lymphoid Tissue during Acute Human Immunodeficiency Virus Type 1 Infection

2002 ◽  
Vol 185 (9) ◽  
pp. 1355-1358 ◽  
Author(s):  
Jan Andersson ◽  
Sabine Kinloch ◽  
Anders Sönnerborg ◽  
Jakob Nilsson ◽  
Thomas E. Fehniger ◽  
...  
2005 ◽  
Vol 12 (12) ◽  
pp. 1416-1424 ◽  
Author(s):  
Kovit Pattanapanyasat ◽  
Surada Lerdwana ◽  
Egarit Noulsri ◽  
Thanyanan Chaowanachan ◽  
Punneeporn Wasinrapee ◽  
...  

ABSTRACT Use of the standard dual-platform flow cytometric method for determination of CD4+ T-lymphocyte counts, which needs both a flow cytometer (FCM) and hematological analyzer, would inevitably lead to increased variability. The development of new single-platform (SP) FCMs that provide direct CD4+ T-lymphocyte counts for improved assay precision and accuracy have recently attracted attention. This study evaluated one of those systems, CyFlowgreen (Partec), a single-parameter SP volumetric FCM. The performance of CyFlowgreen was compared with those of two reference standard SP microbead-based technologies of the three-color TruCOUNT tube with the FACScan FCM and a two-color FACSCount system (Becton Dickinson Biosciences). Absolute CD4+ and CD8+ T-lymphocyte counts in 200 human immunodeficiency virus type 1-seropositive blood specimens were determined. Statistical analysis for correlation and agreement were performed. A high correlation of absolute CD4 counts was shown when those obtained with CyFlowgreen were compared with those obtained with the bead-based three-color TruCOUNT system (R 2 = 0.96; mean bias, −69.1 cells/μl; 95% confidence interval [CI], −225.7 to +87.5 cells/μl) and the FACSCount system (R 2 = 0.97; mean bias, −40.0 cells/μl; 95% CI, −165.1 to +85.1 cells/μl). The correlation of the CD4+ T-lymphocyte counts obtained by the two bead-based systems was high (R 2 = 0.98). Interestingly, CyFlowgreen yielded CD4+ T-lymphocyte counts that were 21.8 and 7.2 cells/μl lower than those obtained with the TruCOUNT and the FACSCount systems, respectively, when CD4+ T-lymphocyte counts were <250 CD4+ T-lymphocyte counts/μl range or 17.3 and 5.8 cells/μl less, respectively, when CD4+ T-lymphocyte counts were <200 cells/μl. The single-parameter CyFlowgreen volumetric technology performed well in comparison with the performance of the standard SP bead-based FCM system. However, a multicenter comparative study is needed before this FCM machine is implemented in resource-limited settings.


2007 ◽  
Vol 81 (12) ◽  
pp. 6563-6572 ◽  
Author(s):  
Raghavan Chinnadurai ◽  
Devi Rajan ◽  
Jan Münch ◽  
Frank Kirchhoff

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) fusion inhibitors blocking viral entry by binding the gp41 heptad repeat 1 (HR1) region offer great promise for antiretroviral therapy, and the first of these inhibitors, T20 (Fuzeon; enfuvirtide), is successfully used in the clinic. It has been reported previously that changes in the 3-amino-acid GIV motif at positions 36 to 38 of gp41 HR1 mediate resistance to T20 but usually not to second-version fusion inhibitors, such as T1249, which target an overlapping but distinct region in HR1 including a conserved hydrophobic pocket (HP). Based on the common lack of cross-resistance and the difficulty of selecting T1249-resistant HIV-1 variants, it has been suggested that the determinants of resistance to first- and second-version fusion inhibitors may be different. To further assess HIV-1 resistance to fusion inhibitors and to analyze where changes in HR1 are tolerated, we randomized 16 codons in the HR1 region, including those making contact with HR2 codons and/or encoding residues in the GIV motif and the HP. We found that changes only at positions 37I, 38V, and 40Q near the N terminus of HR1 were tolerated. The propagation of randomly gp41-mutated HIV-1 variants in the presence of T1249 allowed the effective selection of highly resistant forms, all containing changes in the IV residues. Overall, the extent of T1249 resistance was inversely correlated to viral fitness and cytopathicity. Notably, one HIV-1 mutant showing ∼10-fold-reduced susceptibility to T1249 inhibition replicated with wild type-like kinetics and caused substantial CD4+-T-cell depletion in ex vivo-infected human lymphoid tissue in the presence and absence of an inhibitor. Taken together, our results show that the GIV motif also plays a key role in resistance to second-version fusion inhibitors and suggest that some resistant HIV-1 variants may be pathogenic in vivo.


2001 ◽  
Vol 75 (9) ◽  
pp. 4430-4434 ◽  
Author(s):  
James P. McGettigan ◽  
Heather D. Foley ◽  
Igor M. Belyakov ◽  
Jay A. Berzofsky ◽  
Roger J. Pomerantz ◽  
...  

ABSTRACT Novel viral vectors that are able to induce both strong and long-lasting immune responses may be required as effective vaccines for human immunodeficiency virus type 1 (HIV-1) infection. Our previous experiments with a replication-competent vaccine strain-based rabies virus (RV) expressing HIV-1 envelope protein from a laboratory-adapted HIV-1 strain (NL4–3) and a primary HIV-1 isolate (89.6) showed that RV-based vectors are excellent for B-cell priming. Here we report that cytotoxic T-lymphocyte (CTL) responses against HIV-1 gp160 are induced by recombinant RVs. Our results indicated that a single inoculation of mice with an RV expressing HIV-1 gp160 induced a solid and long-lasting memory CTL response specific for HIV-1 envelope protein. Moreover, CTLs from immunized mice were not restricted to the homologous HIV-1 envelope protein and were able to cross-kill target cells expressing HIV-1 gp160 from heterologous HIV-1 strains. These studies further suggest promise for RV-based vectors to elicit a persistent immune response against HIV-1 and their potential utility as efficacious anti-HIV-1 vaccines.


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