Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes

Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6092-7. doi: 10.1073/pnas.0304860101. Epub 2004 Apr 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis*
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line
  • Dendritic Cells / immunology*
  • HIV Antibodies / chemistry
  • HIV Antigens / immunology*
  • HIV-1 / immunology
  • HIV-1 / physiology
  • Virus Replication

Substances

  • HIV Antibodies
  • HIV Antigens