Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes.
A better understanding of the antigen presentation pathways that lead to CD8(+) T cell recognition of HIV epitopes in vivo is needed to achieve better immune control of HIV replication. Here, we show that cross-presentation of very small amounts of HIV proteins from apoptotic infected CD4(+) T lymphocytes by dendritic cells to CD8(+) T cells is much more efficient than other known HIV presentation pathways, i.e., direct presentation of infectious virus or cross-presentation of defective virus. Unexpectedly, dendritic cells also take up actively antigens into endosomes from live infected CD4(+) T lymphocytes and cross-present them as efficiently as antigens derived from apoptotic infected cells. Moreover, live infected CD4(+) T cells costimulate cross-presenting dendritic cells in the process. Therefore, dendritic cells can present very small amounts of viral proteins from infected T cells either after apoptosis, which is frequent during HIV infection, or not. Thus, if HIV expression is transiently induced while costimulation is enhanced (for instance after IL-2 and IFNalpha immune therapy), this HIV antigen presentation pathway could be exploited to eradicate latently infected reservoirs, which are poorly recognized by patients' immune systems.
Marañón
Concepción
C
Département d'Immunologie, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U567, Unité Mixte de Recherche, Centre National de la Recherche Scientifique 8104, Institut Federatif de Recherche 116, Université Paris V, Paris, France.
Desoutter
Jean-François
JF
Hoeffel
Guillaume
G
Cohen
William
W
Hanau
Daniel
D
Hosmalin
Anne
A
D000595:Amino Acid Sequence; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D015483:HIV Antibodies / Q000737:chemistry; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D014779:Virus Replication
D015483:HIV Antibodies; D015488:HIV Antigens