Monocyte derived dendritic cells from HIV-1 infected individuals partially reconstitute CD4 T-cell responses.
OBJECTIVE
The study tests the hypothesis that monocyte derived dendritic cells from HIV-1 infected individuals are normal and can restore impaired CD4 T-cell antigen specific responses.


METHODS
Monocyte derived dendritic cells were isolated from individuals at three different stages of HIV-1 infection with a wide spectrum of viral load and CD4 T-cell counts, and from healthy volunteers. The cell surface phenotype and allogeneic stimulatory potential of these dendritic cells was documented. CD4 T-cell responses to HIV p24, tetanus toxoid and purified protein derivative were measured using either unfractionated peripheral blood mononuclear cells, or purified dendritic cell/T-cell cultures.


RESULTS
Dendritic cells from all three HIV-1 infected groups did not differ from each other or from healthy volunteers in terms of cell surface phenotype or allogeneic stimulatory potential using T cells from healthy volunteers. Dendritic cells from immunosuppressed antiretroviral naive individuals enhanced the autologous recall proliferative responses both to HIV-1 p24, and third party antigens tetanus toxoid and purified protein derivative, both in terms of the proportion of responding individuals, and median proliferation.


CONCLUSIONS
Antigen presentation by dendritic cells partially restores impaired antigen specific CD4 T-cell responses associated with HIV-1 infection. Immunization strategies which target dendritic cells may therefore offer significant advantages in the ability to stimulate HIV-specific protective immune responses.
Newton
Philippa J
PJ
Department of Immunology and Molecular Pathology, University College London, UK.
Weller
Ian V D
IV
Williams
Ian G
IG
Miller
Robert F
RF
Copas
Andrew
A
Tedder
Richard S
RS
Katz
David R
DR
Chain
Benjamin M
BM
D000328:Adult; D017951:Antigen Presentation / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D013745:Tetanus Toxoid / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D019562:Viral Load
D016655:HIV Core Protein p24; D013745:Tetanus Toxoid; D014373:Tuberculin