HIV-1 upregulates intercellular adhesion molecule-1 gene expression in lymphoid tissue of patients with chronic HIV-1 infection.
OBJECTIVE
Intercellular adhesion molecule (ICAM)-1 is an adhesion molecule that plays an important role in the transmission of HIV-1 to CD4+ target cells and in the decrease of these cells in lymphoid tissue (LT). Our main objective was to study ICAM-1 expression in LT from HIV-1-infected persons and to correlate this expression with LT viral load and the immunoarchitecture alteration before and after highly active antiretroviral therapy (HAART).


METHODS
Tonsillar LT samples from 16 patients with chronic asymptomatic HIV-1 infection were studied before initiating treatment and after 12 months of HAART. ICAM-1 protein expression was studied by immunohistochemistry in all cases, and ICAM-1 messenger RNA (mRNA) was quantified from frozen tissue in 6 patients using quantitative real-time polymerase chain reaction (PCR). LT viral load was determined by PCR. The LT immunoarchitecture, p24 immunoexpression, and CD4+ cell count were assessed from tissue sections.


RESULTS
Before initiating HAART, there was high immunohistochemical ICAM-1 expression in follicular dendritic and endothelial cells and high ICAM-1 mRNA quantification. These findings correlated with a high LT viral load, strong p24 expression, and an effacement of LT immunoarchitecture with a low number of CD4+ cells. After HAART, there was a significant decrease of immunohistochemical and gene ICAM-1 expression. These results correlated with a significant decrease of LT viral load and p24 immunoexpression, a recovery of LT architecture, and a significant increase of CD4+ cells.


CONCLUSIONS
HIV-1 upregulates ICAM-1 expression in LT. This finding is associated with a marked effacement of LT architecture. HAART produces downregulation of ICAM-1 expression and recovery of LT architecture by reducing LT viral load significantly.
Garrido
Marta
M
Department of Pathology, Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Mozos
Anna
A
Martínez
Antonio
A
García
Felipe
F
Serafín
Anna
A
Morente
Vanesa
V
Caballero
Miguel
M
Gil
Cristina
C
Fumero
Emilio
E
Miró
Jose M
JM
Climent
Nuria
N
Gatell
Jose M
JM
Alos
Llucia
L
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology; D014066:Palatine Tonsil / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D015854:Up-Regulation; D019562:Viral Load