1995
DOI: 10.1038/nm0495-330
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Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression

Abstract: An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 nef protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4+ T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4+ cells of the patient were lacking the nef epitope. These results sugg… Show more

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Cited by 354 publications
(216 citation statements)
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“…Epidemiological studies have highlighted the very signi®cant role that strong and persistent cell-mediated immune responses have in the control of retroviral replication and in the maintenance of the symptom-free state (Koup et al, 1994;Borrow et al, 1994;Rinaldo et al, 1995;Ogg et al, 1998;Paxton et al, 1996). These observations have resulted in attempts to modify the outcome of infection in human patients by the adoptive transfer of CD8 T cells of predetermined viral antigen speci®city (Koenig et al, 1995;Brodie et al, 1999). Such immunotherapeutic strategies may prove to be an invaluable adjunct to chemotherapeutic regimes which recent reports suggest are unlikely to completely eliminate reservoirs of virus within the host (Finzi et al, 1999).…”
Section: Introductionmentioning
confidence: 99%
“…Epidemiological studies have highlighted the very signi®cant role that strong and persistent cell-mediated immune responses have in the control of retroviral replication and in the maintenance of the symptom-free state (Koup et al, 1994;Borrow et al, 1994;Rinaldo et al, 1995;Ogg et al, 1998;Paxton et al, 1996). These observations have resulted in attempts to modify the outcome of infection in human patients by the adoptive transfer of CD8 T cells of predetermined viral antigen speci®city (Koenig et al, 1995;Brodie et al, 1999). Such immunotherapeutic strategies may prove to be an invaluable adjunct to chemotherapeutic regimes which recent reports suggest are unlikely to completely eliminate reservoirs of virus within the host (Finzi et al, 1999).…”
Section: Introductionmentioning
confidence: 99%
“…In the viral quasispecies thus formed, HIV variants with functionally crippled nef genes due to in-frame stop codon mutations, deletions or frameshift mutations, have been documented in several patients (Deacon et al 1995;Kirchho¡ et al 1995;Koenig et al 1995;Mariani et al 1996;Price et al 1997;Salvi et al 1998;Schwartz et al 1996;Shugars et al 1993). These forms have been found despite the substantial pressure to maintain an open reading frame (Kestler et al 1991).…”
Section: Introductionmentioning
confidence: 99%
“…However, virusspecific CD8 ϩ T cell immune responses are not equally effective in HIV control, as the majority of infected individuals progress to disease despite the presence of these cells. HIV is able to evade immune responses by developing mutations that mediate escape from CTL recognition (6)(7)(8)(9)(10)(11)(12). In addition, the expression of certain HLA class I molecules by HIV-infected patients, such as HLA-B*27, HLA-B*57, HLA-B*58:01, HLA-B*81:01, and HLA-A*74: 01, is associated with better clinical disease outcomes in some population settings (3,(13)(14)(15)(16)(17)(18).…”
mentioning
confidence: 99%