Increased in vitro tetanus-induced production of HIV type 1 following in vivo immunization of HIV type 1-infected individuals with tetanus toxoid.
We have previously demonstrated that immunization of HIV-1-infected individuals with the common recall antigen, tetanus, induced transient increases in plasma viremia as well as an increased ability to isolate virus from CD8+ T cell-depleted peripheral blood mononuclear cells (PBMCs) under minimally stimulated culture conditions (IL-2 plus IL-4) postimmunization. In this study, HIV-1-infected individuals were immunized with tetanus toxoid and PBMCs were examined at multiple time points following immunization. Tetanus-induced production of virus was defined as an increased ability to isolate HIV-1 from CD8+ T cell-depleted PBMCs in vitro in the presence of tetanus antigen as opposed to no antigen or control antigen alone. Following immunization, in vitro tetanus-induced production of HIV-1 was observed in 8 of 13 (62%) patients compared to 2 of 13 (15%) patients prior to immunization. In four of these patients, virus could also be isolated from CD8+ T cell-depleted PBMCs in the presence of tetanus without the addition of any exogenous IL-2. Furthermore, virus could be isolated from the unfractionated PBMCs of two patients when tetanus antigen alone was added to the culture in the absence of added PHA or PHA blasts. HIV-1 was isolated predominantly from CD4+ T cells with a CD45RO+, CD25+ phenotype and was associated with a trend to elevated levels in culture supernatants of IFN-gamma, IL-6, TNF-alpha, and IL-4. These findings have important implications with regard to the role of ongoing antigen-specific immune responses in the induction of HIV-1 expression in vivo.
Ostrowski
M A
MA
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Stanley
S K
SK
Justement
J S
JS
Gantt
K
K
Goletti
D
D
Fauci
A S
AS
D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007114:Immunization; D013745:Tetanus Toxoid / Q000276:immunology*
D013745:Tetanus Toxoid