Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia.
BACKGROUND
HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.


METHODS
To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA.


RESULTS
Overall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.


CONCLUSIONS
Strong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.
Zhou
Li
L
Retroviral Genetics Division, Center for Virus Research, Westmead Millennium Institute, Westmead Hospital, The University of Sydney, Westmead, NSW, Sydney, Australia. juile_zhou@wmi.usyd.edu.au
Rua
Rejane
R
Ng
Thomas
T
Vongrad
Valentina
V
Ho
Yung S
YS
Geczy
Carolyn
C
Hsu
Kenneth
K
Brew
Bruce J
BJ
Saksena
Nitin K
NK
D015526:AIDS Dementia Complex / Q000276:immunology* / Q000473:pathology; D000328:Adult; D001483:Base Sequence; D001921:Brain / Q000276:immunology / Q000473:pathology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002675:Child, Preschool; D005260:Female; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction
D016655:HIV Core Protein p24; C514799:p24 protein, Human Immunodeficiency Virus Type 1