Interleukin-10-secreting CD4 cells from aged patients with... : AIDS (original) (raw)

CLINICAL SCIENCE

Interleukin-10-secreting CD4 cells from aged patients with AIDS decrease in-vitro HIV replication and tumour necrosis factor α production

Andrade, Regis Ma; Lima, Patrícia Gc; Filho, Renato GSc; Hygino, Joanac; Milczanowski, Samantha Fd; Andrade, Arnaldo FBd; Lauria, Catharinae; Brindeiro, Rodrigob; Tanuri, Amilcarb; Bento, Cleonice AMc

From the aDepartment of Infectious Diseases, Brazil

bDepartment of Genetics, Brazil

cDepartment of Microbiology and Parasitology, Federal University of Rio de Janeiro, Brazil

dDepartment of Microbiology, Immunology and Parasitology, Brazil

eUniversity Hospital, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Received 12 January, 2007

Revised 1 June, 2007

Accepted 7 June, 2007

Correspondence to Dr C.A.M. Bento, Department of Microbiology and Parasitology, Federal University of Rio de Janeiro, Frei Caneca 94, 20.261-040, Rio de Janeiro, Brazil. E-mail: [email protected]

Abstract

Objective:

To evaluate the impact of age on the proliferative response, cytokine profile and viral kinetics in AIDS patients treated successfully with antiretroviral drugs.

Methods:

Peripheral blood mononuclear cells (PBMC), CD4 cell-depleted PBMC or CD4 T cells from young adult and aged HIV-1-infected patients were activated in vitro with anti-CD3 with or without interleukin (IL)-2. Lymphoproliferation and cytokines were measured after 3 days and in-vitro HIV-1 replication after 7 days.

Results:

Both lymphoproliferation and cytokine [IL-1β, tumour necrosis factor α (TNF-α) and interferon γ (IFN-γ)] secretion were higher in younger than in older AIDS patients. In cultures of cells derived from aged patients and activated by anti-CD3, IFN-γ production was severely damage and IL-10 production was much higher. Although IL-2 addition to activated PBMC elevated IFN-γ secretion, IL-10 production remained elevated in the aged group. The depletion of CD4 T lymphocytes from these cultures dramatically reduced released IL-10 in the older group but did not alter significantly IFN-γ production. Interestingly, higher IL-10 levels produced by CD4 T cells were related to lower in-vitro HIV-1 replication, and the blockade of this cytokine by anti-IL-10 monoclonal antibody enhanced virus replication. This effect may be correlated with elevated TNF-α secretion. Finally, impaired IFN-γ secretion detected in activated CD4 T cells obtained from aged patients was not directly correlated with high IL-10 production.

Conclusions:

Elevated IL-10 production by aged AIDS patients contributed considerably to control of HIV replication and to inhibition of TNF-α secretion but not to the reduced IFN-γ production.