Early immune activation in gut-associated and peripheral lymphoid tissue during acute HIV infection

Abstract

To study innate and adaptive immune responses in gut-associated lymphoid tissue (GALT) as well as peripheral lymphoid tissue (pLT) obtained from individuals with acute HIV-1 infection syndrome. The expression of chemokines [regulated upon activation: normal T cell expressed/secreted (RANTES), macrophage-inflammatory protein (MIP) 1alpha/beta], cytokines (IL-1beta, TNF-alpha, IL-12, IL-4, IL-10, IL-2, IFN-gamma) and cytotoxic effector molecules (granzyme A, perforin) and cell marker (CD8) were analysed at the single cell level in GALT and pLT of patients experiencing acute HIV-1 infection (day -3 to 48 days from onset of acute symptoms). Substantial pro-inflammatory immune responses (TNF-alpha, IL-1beta, IL-12) and expansion in the CD8 T-cell population were noted in both compartments compared with uninfected controls. This was associated with an early increased expression of beta-chemokines (RANTES, MIP-1alpha/beta) and granzyme, but not with an increase in the expression of perforin. The upregulation of IL-2, IL-12 and IL-4 was noted in both pLT and GALT, whereas IL-10 expression was mainly increased in GALT. Taken together, these findings demonstrate that there was a broad and early immune activation in GALT and pLT during acute HIV-1 infection. The relative lack of perforin expression in both GALT and pLT, however, questions the functional efficacy of the observed immune activation in generating cytotoxic T cells that were able to eliminate HIV-infected cells.