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Secretion by Activated T Cells in HIV-1 Infection Associated with Viral Suppression and a Lack of Disease Progression1
*
Wistar Institute, Philadelphia, PA 19104;
Philadelphia Field Initiating Group for HIV Trials, Philadelphia, PA 19107; and
Johns Hopkins School of Public Health, Baltimore, MD 21205
The immunopathology of HIV-1 infection includes immune defects in T
cell cytokine secretion, resulting in decreased Ag-specific responses.
In this report, IL-13 and IFN-
were analyzed in progressive HIV-1
disease. Both cytokines exert positive effects on Ag presentation and
inhibit HIV-1 infection of macrophages.
Anti-CD3/anti-CD28-activated PBMC from HIV-1-infected individuals
(n = 74) compared with uninfected subjects
(n = 30) secreted significantly less IL-13 (median,
0.64 ng/ml vs 2.07 ng/ml; p < 0.001) and IFN-
(median, 40.96 ng/ml vs 129.5 ng/ml; p < 0.005).
Decreased IL-13 and IFN- secretion in HIV infection was present in
sorted CD4+ and CD8+ T cell subsets, and
additional analysis determined concurrent deficiency at the protein and
transcriptional level. Longitudinal analysis showed that cytokine
secretion levels correlated positively with CD4 count and negatively
with plasma HIV-1 viral load. Patients changing to suppressive
antiretroviral therapy during the study showed increases in IL-13 and
IFN- secretion. Overall, results show a decline in IL-13 and IFN-
secretion in progressive HIV-1 infection and suggest a role for both
cytokines as part of T cell adaptive responses associated with a lack
of disease progression.
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