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.
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ABSTRACT: The great variability of protein sequences from human immunodeficiency virus (HIV) type 1 (HIV-1) isolates represents a major obstacle to the development of an effective vaccine against this virus. The surface protein (Env), which is the predominant target of neutralizing antibodies, is particularly variable. Here we examine the impact of variability among different HIV-1 subtypes (clades) on cytotoxic T-lymphocyte (CTL) activities, the other major component of the antiviral immune response. CTLs are produced not only against Env but also against other structural proteins, as well as some regulatory proteins. The genetic subtypes of HIV-1 were determined for Env and Gag from several patients infected either in France or in Africa. The cross-reactivities of the CTLs were tested with target cells expressing selected proteins from HIV-1 isolates of clade A or B or from HIV type 2 isolates. All African patients were infected with viruses belonging to clade A for Env and for Gag, except for one patient who was infected with a clade A Env-clade G Gag recombinant virus. All patients infected in France were infected with clade B viruses. The CTL responses obtained from all the African and all the French individuals tested showed frequent cross-reactions with proteins of the heterologous clade. Epitopes conserved between the viruses of clades A and B appeared especially frequent in Gag p24, Gag p18, integrase, and the central region of Nef. Cross-reactivity also existed among Gag epitopes of clades A, B, and G, as shown by the results for the patient infected with the clade A Env-clade G Gag recombinant virus. These results show that CTLs raised against viral antigens from different clades are able to cross-react, emphasizing the possibility of obtaining cross-immunizations for this part of the immune response in vaccinated individuals.Journal of Virology 06/1998; · 5.08 Impact Factor
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ABSTRACT: Cytotoxic T lymphocytes (CTLs) are thought to play a crucial role in the termination of the acute primary HIV-1 syndrome, but clear evidence for this presumption has been lacking. Here we demonstrate positive selection of HIV-1 proviral sequences encoding variants within a CTL epitope in Nef, a gene product critical for viral pathogenicity, during and after seroconversion. These positively selected HIV-1 variants carried epitope sequence changes that either diminished or escaped CTL recognition. Other proviruses had mutations that abolished the Nef epitope altogether. These results provide clear evidence that CTLs exert selection pressure on the viral population in acute HIV-1 infection.Proceedings of the National Academy of Sciences 04/1997; 94(5):1890-5. · 9.74 Impact Factor
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ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) Env-, Gag-, Pol-, Nef-, and Tat-specific cytotoxic T-lymphocyte (CTL) activities were quantitated temporally in five patients with symptomatic primary HIV-1 infection. A dominant CD8(+)-mediated, major histocompatibility complex class I-restricted CTL response to the HIV-1 envelope glycoprotein, gp160, was noted in four of the five patients studied. The level of HIV-1-specific CTL activity in the five patients paralleled the efficiency of control of primary viremia. Patients who mounted strong gp160-specific CTL responses showed rapid reduction of acute plasma viremia and antigenemia, while in contrast, primary viremia and antigenemia were poorly controlled in patients in whom virus-specific CTL activity was low or undetectable. These results suggest that HIV-1-specific CTL activity is a major component of the host immune response associated with the control of virus replication following primary HIV-1 infection and have important implications for the design of antiviral vaccines.Journal of Virology 10/1994; 68(9):6103-10. · 5.08 Impact Factor