Abstract
One factor in the development of neuroAIDS is the increase in the migration of pro-inflammatory CD8 T cells across the blood–brain barrier. Typically these cells are involved with keeping the viral load down. However, the persistence of above average numbers of CD8 T cells in the brain, not necessarily specific to viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma chain (γc) cytokines. Here, using the non-human primate model of neuroAIDS, we have demonstrated that exposure to methamphetamine, a powerful illicit drug that has been associated with HIV exposure and neuroAIDS severity, can cause an increase in molecules of the γc system. Among these molecules, IL15, which is upregulated in astrocytes by methamphetamine, and that induces the proliferation of T cells, may also be involved in driving an inflammatory phenotype in innate immune cells of the brain. Therefore, methamphetamine and IL15 may be critical in the development and aggravation of central nervous system immune-mediated inflammatory pathology in HIV-infected drug abusers.
Highlights
The immunological environment of the central nervous system (CNS) is highly susceptible to changes due to a number of insults, such as infections that cross the blood–brain barrier (BBB), or even related peripheral changes
We found that the expression of IL2RG, used by all common gamma chain cytokines, exhibited a highly significant upregulation pattern in simian immunodeficiency virus (SIV) compared to control (p = 0.000045), and in SIV/Meth compared to SIV (p = 0.0001)
In the context of neuroAIDS, we have reported the involvement of IL15 in maintaining the presence of activated CD8 T cells chronically in the CNS (Marcondes et al, 2007)
Summary
The immunological environment of the central nervous system (CNS) is highly susceptible to changes due to a number of insults, such as infections that cross the blood–brain barrier (BBB), or even related peripheral changes. Glial activation and the development of a pro-inflammatory cytokine environment favor the accumulation of activated CD8 T cells and macrophages (Marcondes et al, 2001, 2007) These changes in the brain are associated to the development of deficits in motor and cognitive abilities, and other disruptions such as in the circadian rhythm of body temperature and sleep patterns (Marcondes et al, 2001; Huitron-Resendiz et al, 2007). A large number of HIV-infected individuals acquire the virus from Meth use or are exposed to this drug during disease course (Mathers et al, 2008). Both HIV infection and Meth dependence can be associated with brain dysfunction. Viral burden in the brain and inflammatory neuropathology associated with HIV infection are drastically aggravated by Meth use (Everall et al, 2005), which contributes to the severity of neuroAIDS
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