Interleukin-10-secreting CD4 cells from aged patients with AIDS decrease in-vitro HIV replication and tumour necrosis factor alpha production.
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-1beta, tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma)] secretion were higher in younger than in older AIDS patients. In cultures of cells derived from aged patients and activated by anti-CD3, IFN-gamma production was severely damage and IL-10 production was much higher. Although IL-2 addition to activated PBMC elevated IFN-gamma 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-gamma 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-alpha secretion. Finally, impaired IFN-gamma 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-alpha secretion but not to the reduced IFN-gamma production.
Andrade
Regis M
RM
Department of Infectious Diseases, Federal University of Rio de Janeiro, Brazil.
Lima
Patrícia G
PG
Filho
Renato G S
RG
Hygino
Joana
J
Milczanowski
Samantha F
SF
Andrade
Arnaldo F B
AF
Lauria
Catharina
C
Brindeiro
Rodrigo
R
Tanuri
Amilcar
A
Bento
Cleonice A M
CA
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014779:Virus Replication
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma