Markers of cell death-activation in lymphocytes of vertically HIV-infected children naive to highly active antiretroviral therapy: the role of age.
BACKGROUND
Apoptosis plays a major role in depleting CD4(+) lymphocytes during infection with HIV-1. Few data exist on its role during HIV infection of children. Sensitivity of peripheral blood lymphocytes (PBLs) to apoptotic stimuli and the importance of the patient's age remain unclear.


OBJECTIVE
We sought to analyze the following: (1) markers of cell death-activation (CD95, CD45 isoforms, and CD28) in PBLs from vertically HIV-infected children of different ages before highly active antiretroviral therapy; (2) changes in other PBL populations; (3) PBL sensitivity to cell death and mitochondrial damages; and (4) role of age during progression of infection.


METHODS
Cell culture techniques and flow cytometry were used to analyze surface antigens, PBL susceptibility to apoptosis, or PBL susceptibility to change of mitochondrial membrane potential.


RESULTS
Donor age had a strong negative correlation with numbers of CD4(+) and CD8(+) T cells. Virgin T lymphocyte (CD45RA(+), CD95(-)) levels and those of CD95(+) cells showed no correlation with the children's clinical status but did show a correlation with patient age. CD28(-) T lymphocytes were markedly augmented in HIV-infected children but were unrelated to stage of infection or age. A relevant decrease in B lymphocytes and an increase in natural killer cells were also found. Finally, PBLs from HIV-positive children had a marked tendency to undergo apoptosis and mitochondrial damage.


CONCLUSIONS
Changes in PBL phenotype, increased expression of CD95, and high sensitivity to apoptosis suggest that a precocious aging of the immune system occurs in HIV-infected children.
Viganò
A
A
Department of Pediatrics IV, University of Milano School of Medicine, Milan, Italy.
Pinti
M
M
Nasi
M
M
Moretti
L
L
Balli
F
F
Mussini
C
C
Bricalli
D
D
Sala
N
N
Bugarini
R
R
Vella
S
S
Principi
N
N
Cossarizza
A
A
D000293:Adolescent; D000367:Age Factors; D000945:Antigens, Differentiation, T-Lymphocyte / Q000302:isolation & purification*; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D018106:CD28 Antigens / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D017493:Leukocyte Common Antigens / Q000302:isolation & purification; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000302:isolation & purification
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D019014:fas Receptor; D017493:Leukocyte Common Antigens