Effect of HIV vertical transmission on the ontogeny of T cell antigens involved in the regulation of humoral immune response.
HIV infection causes progressive impairment of humoral immunity, including defective specific antibody production. To evaluate whether vertical HIV infection interferes with the expression on CD4+ lymphocytes of developmentally regulated molecules, that play a crucial role in the generation of immunological memory (CD45 isoforms) and in attainment of antibody responses (CD40L), 22 HIV-infected children and 36 seroreverted children born to HIV+ mothers were studied. The percentage of CD40L+ PBMC after activation in vitro with phorbol myristate acetate (PMA) plus ionomycin was lower in HIV-infected children than in controls (P < 0.004). This correlated with the depletion of CD4+ lymphocytes (r = 0.75; P < 0.001). CD40L expression rose progressively with age (r = 0.36; P = 0.03) in seroreverted children, but not in HIV-infected children, suggesting that while in normal children in vivo antigen stimulation results in progressive attainment of CD40L expression (and thus to effective T-B cell cooperation), this process is largely defective in HIV-infected children, contributing to the genesis of humoral immune deficiency. The proportion of CD4+ cells bearing the CD45RO isoform was increased among HIV-infected infants during the first years of life. However, the percentage of CD4+ CD45RO+ peripheral blood mononuclear cells (PBMC) progressively increased with age in controls (r = 0.69; P = 0.03), but not in HIV-infected children, showing that while vertical transmission of HIV does not prevent CD45RO expression early in life, it is associated with a disturbance of the physiological process of antigen priming, contributing to poor immunological memory to T cell-dependent antigens.
Brugnoni
D
D
Clinical Immunology Service, Spedali Civili, Brescia, Italy.
Soresina
A
A
Airo
P
P
Ugazio
A G
AG
Notarangelo
L D
LD
Cattaneo
R
R
Duse
M
M
D000367:Age Factors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D002648:Child; D002675:Child, Preschool; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000151:congenital* / Q000635:transmission; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D017493:Leukocyte Common Antigens