Antigen-driven C-C chemokine-mediated HIV-1 suppression by CD4(+) T cells from exposed uninfected individuals expressing the wild-type CCR-5 allele.
Despite repeated exposure to HIV-1, certain individuals remain persistently uninfected. Such exposed uninfected (EU) people show evidence of HIV-1-specific T cell immunity and, in rare cases, selective resistance to infection by macrophage-tropic strains of HIV-1. The latter has been associated with a 32-base pair deletion in the C-C chemokine receptor gene CCR-5, the major coreceptor of macrophage-tropic strains of HIV-1. We have undertaken an analysis of the HIV-specific T cell responses in 12 EU individuals who were either homozygous for the wild-type CCR-5 allele or heterozygous for the deletion allele (CCR-5Delta32). We have found evidence of an oligoclonal T cell response mediated by helper T cells specific for a conserved region of the HIV-1 envelope. These cells produce very high levels of C-C chemokines when stimulated by the specific antigen and suppress selectively the replication of macrophage-tropic, but not T cell-tropic, strains of HIV-1. These chemokine-producing helper cells may be part of a protective immune response that could be potentially exploited for vaccine development.
Furci
L
L
Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy.
Scarlatti
G
G
Burastero
S
S
Tambussi
G
G
Colognesi
C
C
Quillent
C
C
Longhi
R
R
Loverro
P
P
Borgonovo
B
B
Gaffi
D
D
Carrow
E
E
Malnati
M
M
Lusso
P
P
Siccardi
A G
AG
Lazzarin
A
A
Beretta
A
A
D000483:Alleles; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018925:Chemokines / Q000096:biosynthesis / Q000502:physiology*; D002999:Clone Cells; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000235:genetics*; D015728:Receptors, HIV / Q000235:genetics*; D014779:Virus Replication / Q000276:immunology
D019380:Anti-HIV Agents; D018925:Chemokines; D015699:HIV Envelope Protein gp120; D010455:Peptides; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV