Adenovirus vector-specific T cells demonstrate a unique memory phenotype with high proliferative potential and coexpression of CCR5 and integrin alpha4beta7.
BACKGROUND
The Step Study was a randomized trial to reduce HIV infection through vaccination with an adenovirus type 5 (Ad5)-based gag/pol/nef construct; analysis following early cessation of the trial revealed an excess of HIV seroconversion in Ad5 seropositive men. This led to the suggestion that the Ad based vector may boost the number of CD4 chemokine receptor 5 (CCR5) T cells, target cells for HIV infection.


OBJECTIVE
We sought to determine the immunophenotype and proliferative capacity of Ad5-specific T cells in the peripheral blood of adult donors to determine whether stimulation with replication defective Ad5 vectors could result in the significant expansion of a CD4 CCR5 T-cell subset.


METHODS
Ad5-specific T cells were identified in the peripheral blood of healthy donors by interferon-gamma secretion assay and proliferative response was measured by carboxyfluorescein succinimidyl ester labelling. Cells were analyzed by flow cytometry to determine T-cell differentiation marker, CCR5 and alpha4beta7 expression on memory and proliferated cells.


RESULTS
Ad5-specific CD4 T cells within healthy adult donors exhibit a unique minimally differentiated memory phenotype with coexpression of CD45RA, CD45RO and CCR7. Stimulation with Ad vector leads to rapid expansion in vitro and a switch to an effector memory phenotype. Both short-term reactivated and proliferating Ad5-specific CD4 T cells express the HIV coreceptor CCR5 and the HIV gp120-binding integrin alpha4beta7.


CONCLUSIONS
Ad5-specific T cells demonstrate a phenotype and proliferative potential that would support HIV infection; these results are pertinent to the findings of the Step Study and future use of Ad5 as a vaccine vector.
Chakupurakal
Geothy
G
University of Birmingham, Birmingham, UK.
Onion
David
D
Cobbold
Mark
M
Mautner
Vivien
V
Moss
Paul A H
PA
D000260:Adenoviruses, Human / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000635:transmission*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping / Q000379:methods; D016023:Integrins / Q000378:metabolism*; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism*
D016023:Integrins; D019713:Receptors, CCR5; C071777:integrin alpha4beta7