Association between HIV Type 1-specific T cell responses and CD4+ T cell counts or CD4+:CD8+ T cell ratios in HIV Type 1 subtype B infection in China.
ABSTRACT CD4+ T cell counts and CD4+:CD8+ T cell ratios represent key determinants of HIV disease progression and infectivity. However, the relationship between the HIV-1-specific cytotoxic T lymphocyte (CTL) response and these determinants has not been elucidated for all HIV-1B and HIV-1C proteins. In the present study, virusspecific T cell responses to HIV-1B and HIV-1C proteins were analyzed with interferon gamma (IFN-gamma) enzyme- linked immunospot (ELISpot) assays using synthetic overlapping peptides corresponding to naturally occurring HIV-1B and HIV-1C consensus sequences. For Gag/Gag p24/Gag p17, a correlation between T cell responses and CD4+ T cell count in HIV-1 clade B and clade C was seen: elevated T cell response resulted in higher CD4+ T cell production. A statistically significant correlation between the Pol-specific T cell response and CD4+ T cell counts was also found in HIV-1 subtype C. For all HIV-1B and HIV-1C proteins, a correlation between the HIV-1-specific T cell response and CD4+:CD8+ T cell ratios was found for Tat and Pol proteins. CD4+ T cell counts in patients with Tat and/or Rev T cell response were higher than in patients without Tat and/or Rev T cell response. We suggest that this correlation within HIV-1B and HIV-1C Gag p24/Gag p17 responses makes the Gag p24/Gag p17 region a potential vaccine candidate and that HIV-1-specific CTL epitopes toward Pol are important in controlling HIV-1 infection; we emphasize that future vaccination strategies should include these early antigens, Tat and Rev.
- SourceAvailable from: Kee-Jong Hong
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- "Thus, the relationship between immune components and virological events in HIV-1 infection remains controversial. The factors leading to different conclusions from each research group might include varying parameters of each study population, such as ethnic differences, clinical status or the different genetic traits of HIV strains [10,13]. "
ABSTRACT: HIV-1 specific cytotoxic T lymphocytes (CTLs) have an important role as antiviral effector cells for controlling HIV-1 infection. To investigate CTL response during the early stage of HIV infection, we measured immunity-related factors including CD4+ T cell counts, CD8+ T cell counts, HIV-1 RNA viral loads and IFN-γ secretion according to CTL response in 78 selected primary HIV-1-infected Koreans. The CTL response was strongly induced by HIV-1 specific Gag and Nef peptides (p = 0.016) compared with induction by Tat or Env peptides. These results suggest that the major antiviral factors inducing strong HIV-specific CTL responses are associated with the Gag and Nef viral regions in primary HIV-1 infected Koreans. The relationship between viral load and CTL response showed varying correlations with time following HIV infection. CTL response was inversely correlated with viral loads at preseroconversion stage I (r = -0.224 to -0.33) and changed to a positive correlation at the preseroconversion stage II (r = 0.132 to 0.854). Finally, it changed to an inverse correlation again after seroconversion until a viral set point was established on serological profiling (r = -0.195 to -0.407). These findings demonstrate a dynamic correlation between viral load and subsequent CTL responses during early HIV infection.Virology Journal 09/2010; 7:239. DOI:10.1186/1743-422X-7-239 · 2.18 Impact Factor
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- "Walker et al., 1986), CTL lines or CTL clones (Ali et al., 2004; Chung et al., 2007; Loffredo et al., 2006, 2005; Lu and Andrieu, 2001; van Baalen et al., 2002; Yang et al., 2003b) have shown the potential to measure and analyze CTL activities in vitro. Data from a number of in vitro studies using these methods have suggested a positive association between viral antigen-induced cytokine and/or proliferative responses by CTL in vitro and virus control in vivo in humans (Day et al., 2007; Edwards et al., 2002; Wang et al., 2006); the correlation is, however, not absolute. The situation is even more controversial for SIV, with a positive correlation between cytokine expression and control of viral replication shown for some CTL clones and no correlation with others (Chung et al., 2007; Loffredo et al., 2006). "
ABSTRACT: CD8(+) cytotoxic T lymphocyte (CTL) responses play an important role in controlling the replication of primate lentiviruses. Induction of these responses is a key objective for most current AIDS vaccine approaches. Despite a variety of approaches for measuring properties and activities of CTL, the functions responsible for controlling viral replication in vivo have not been clearly identified. Assays measuring CTL-mediated suppression of viral replication in vitro are beginning to be used as possible correlates of in vivo virus suppressive activity, but the utility and interpretive value of these assays are typically limited by properties of the cells that have been used. We investigated the capacity of SIV-specific CTL clones (effectors), immortalized by transduction with human telomerase reverse transcriptase (hTERT), to suppress SIV replication in autologous hTERT immortalized CD4(+) T-cell clones (targets). Immortalized and non-immortalized SIV-specific effector cells showed IFN-gamma production and degranulation in response to viral antigen specific stimulation and significantly inhibited SIV(mac)239 replication (2 to 4 log decrease in viral RNA or cell-associated proviral DNA) (p<0.0005). Our in vitro assays of inhibition of viral replication, using T-cell clones as effectors and targets, provide a well-defined approach for evaluating possible mechanisms of CTL-mediated control of viral production which may involve direct killing of infected target cells and/or release of proinflammatory cytokines such as IFN-gamma and TNF-alpha. The use of hTERT immortalized effector and target cells for such assays preserves relevant functional properties while providing a convenient, reproducible means of conducting studies over time.Virology 04/2008; 372(2):430-41. DOI:10.1016/j.virol.2007.11.013 · 3.32 Impact Factor
Conference Paper: Advances in Crystal Oscillator and Resonator Compensation18th Annual Symposium on Frequency Control. 1964; 02/1964