Pertussis toxin B-oligomer dissociates T cell activation and HIV replication in CD4 T cells released from infected lymphoid tissue.
OBJECTIVE
To investigate, in human lymphoid tissue infected with HIV-1 ex vivo, the immunostimulatory and HIV inhibitory properties of pertussis toxin B oligomer (PTX-B) and of the genetically modified non-toxic PT-9K/129G.


METHODS
Human tonsils from uninfected donors were infected ex vivo with R5 or X4 HIV-1 in the presence or absence of PTX-B. Virus replication was evaluated in culture supernatants; cells emigrated from tissue blocks were immunostained for lymphocytic and activation markers. HIV DNA and cell proliferation were evaluated with real-time PCR and [H]thymidine incorporation, respectively.


RESULTS
Both PTX-B and PT-9K/129G inhibited HIV-1 replication. These compounds activated and stimulated the proliferation of emigrated cells, most of which were CD4 T lymphocytes. Cells emigrated from infected tissues did not produce detectable virus in unstimulated or in PTX-B- or PT-9K/129G-stimulated cultures whereas robust virus production was triggered by phytohemagglutinin (PHA) or interleukin-2 (IL-2). Analysis of HIV DNA content indicated that infected cells were present among emigrated cells and that their number greatly increased following IL-2 stimulation, whereas it remained constant in the presence of PTX-B or PT-9K/129G.


CONCLUSIONS
PTX-B and PT-9K/129G inhibit both R5 and X4 HIV-1 replication in human lymphoid tissue ex vivo. In contrast to PHA and IL-2, they promote the proliferation of CD4 T lymphocytes emigrated from tissue, including HIV-infected cells, without triggering virus replication. Therefore, these emigrated CD4 T cells represent a novel model of a latent inducible HIV reservoir. Thus, PTX-B and the clinically approved PT-9K/129G are potential antiretroviral agents endowed with immunostimulatory capacity.
Alfano
Massimo
M
AIDS Immunopathogenesis Unit, Department of Immunology and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Grivel
Jean-Charles
JC
Ghezzi
Silvia
S
Corti
Davide
D
Trimarchi
Matteo
M
Poli
Guido
G
Margolis
Leonid
L
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D014066:Palatine Tonsil / Q000276:immunology / Q000821:virology; D037342:Pertussis Toxin / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D037342:Pertussis Toxin