Early HIV-1 Envelope-specific Cytotoxic T Lymphocyte Responses in Vertically Infected Infants

Abstract

High frequencies of cytotoxic T lymphocyte precursors (CTLp) recognizing HIV-1 laboratory strain gene products have been detected in adults within weeks of primary infection. In contrast, HIV-1–specific CTLp are uncommonly detected in infants younger than 6 mo. To address the hypothesis that the use of target cells expressing laboratory strain env gene products might limit the detection of HIV-1 env-specific CTLp in early infancy, recombinant vaccinia vectors (vv) expressing HIV-1 env genes from early isolates of four vertically infected infants were generated. The frequencies of CTLp recognizing target cells infected with vv-expressing env gene products from early isolates and HIV-1 IIIB were serially measured using limiting dilution followed by in vitro stimulation with mAb to CD3. In one infant, the detection of early isolate env-specific CTLp preceded the detection of IIIB-specific CTLp. CTLp recognizing HIV-1 IIIB and infant isolate env were detected by 6 mo of age in two infants. In a fourth infant, HIV-1 IIIB env and early isolate env-specific CTLp were simultaneously detected at 12 mo of age. These results provide evidence that young infants can generate HIV-1–specific CTL responses and provide support for the concept of neonatal vaccination to prevent HIV-1 transmission. However, the early predominance of type-specific CTL detected in some young infants suggests that the use of vaccines based on laboratory strains of HIV-1 may not protect against vertical infection.

Human Cytomegalovirus Proteins pp65 and Immediate Early Protein 1 Are Common Targets for CD8+ T Cell Responses in Children with Congenital or Postnatal Human Cytomegalovirus Infection

“…HIV-1 specific CD8 ϩ T cells have been infrequently detected in young infants (37,38), possibly due to HIV-1-induced CD4 ϩ T cell dysfunction (39) or viral sequence variation (40). In a recent study of four neonates with asymptomatic congenital HCMV infection, Marchant et al (41) detected HCMV-specific CD8 ϩ T cell responses to a limited number of MHC class I-restricted viral epitopes commonly detected in adults with latent HCMV infection.…”

A stable latent reservoir for HIV-1 in resting CD4+ T lymphocytes in infected children

“…In children who acquire HIV-1 from their mothers, infection is established in the setting of a developing T-cell repertoire, in the presence of high levels of viral replication, and in the presence of deficient cytotoxic T-cell activity (17)(18)(19)(20)(21)(22), and it might even be expected that the frequency of resting CD4 + T cells with integrated HIV-1 would be higher in infected children. In adults, most of the latent virus in resting CD4 + T cells resides in cells with a memory phenotype (23).…”

Autologous Neutralizing Antibody to Human Immunodeficiency Virus-1 and Replication-Competent Virus Recovered from CD4+T-Cell Reservoirs in Pediatric HIV-1–Infected Patients on HAART

“…Other earlier studies in adult LTNP have shown the ability to neutralize primary isolates and heterologous viruses better than those with disease progression. 4,25 However, Montefiori and colleagues 26 found LTNP were unable to neutralize their replicationcompetent HIV with concurrent autologous serum, which differs from our pediatric subjects on HAART who had detectable ANAB to concurrent RCV. Variation in the ability to mount a NAB response to autologous virus may be a reflection of viral diversity and selective pressure on HIV.…”