T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV.
Cell-mediated immunity and T-lymphocyte maturation are impaired in HIV-infected children. These abnormalities would be detected in HIV-uninfected offspring of HIV women (seroreverters [SR]) if HIV or its soluble proteins could cross the placental barrier. Immunophenotypic analyses were performed in 20 healthy HIV-uninfected newborns of HIV-infected mothers (SR), and in 14 healthy newborns of HIV-negative women (UC). The same analyses were performed in 3 groups of older children: SR (n = 41); UC (n = 15); and HIV-infected children (n = 25). Antigen-specific cells were evaluated with ELISpot and fluorimetric analyses; IL-7 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that in SR newborns: (1) the CD4/CD8 ratio was reduced, (2) CD4(+) and CD8(+) naive T-cell percentages were decreased, (3) percentage of activated CD8(+) T cells was increased, and (4) percentages of CD3(+)/4(-)/8(-) (DN) and DN/25(-)/44(+) were augmented. These abnormalities were partially retained in older SR children. CD4(+) and CD8(+) HIV-specific cells were detected in a portion of newborn SRs but not in older SRs. Serum IL-7 was augmented both in newborn and older SRs. Cell-mediated immunity and T-cell maturation are altered even in HIV-uninfected newborns of HIV-infected mothers; these abnormalities persist over time. The biologic significance of these observations and potential subsequent clinical events should be investigated in larger cohorts of seroreverters. (Blood. 2000;96:3866-3871)
Clerici
M
M
Cattedra di Immunologia, Università di Milano, DISP LITA Vialba, Milano, Italy. mago@mailserver.unimi.it
Saresella
M
M
Colombo
F
F
Fossati
S
S
Sala
N
N
Bricalli
D
D
Villa
M L
ML
Ferrante
P
P
Dally
L
L
Vigano'
A
A
D000328:Adult; D000367:Age Factors; D000954:Antigens, Surface / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D019302:HIV Envelope Protein gp160 / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D006679:HIV Seropositivity; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007371:Interferon-gamma / Q000378:metabolism; D015851:Interleukin-7 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009035:Mothers; D013601:T-Lymphocytes / Q000473:pathology*
D000954:Antigens, Surface; D015704:CD4 Antigens; D019302:HIV Envelope Protein gp160; D015851:Interleukin-7; D008934:Mitogens; D007371:Interferon-gamma