AEGiS-14IAC: Magnitude and breadth of pediatric CD8+ T cell responses against HIV are critically influenced by age, viral load and CD4 counts.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Magnitude and breadth of pediatric CD8+ T cell responses against HIV are critically influenced by age, viral load and CD4 counts.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10081)

Sandberg JK, Fast NM, Jordan KA, Furlan SN, Barbour J, Fennelly G, Dobroszycki J, Wiznia A, Spiegel HM, Rosenberg MG, Nixon DF
Gladstone Institute of Virology and Immunology, University of California, San Francisco, United States

BACKGROUND: The immunology of HIV transmission from mother-to-infant differs from that of adult infection in that the immune system of the newborn child is not fully matured. The factors that influence cellular immune responses against HIV in children is largely unknown, although this route of transmission is still common in third world countries.

METHODS: We have investigated the CD8+ T cell response against HIV antigens in peripheral blood of 60 pediatric patients infected at birth. We have measured interferon-[gamma] production in a recombinant vaccinia ELISPOT assay, and the frequency and phenotype of HIV/Gag HLA-A2 tetramer staining cells in a 6-color flow cytometry assay.

RESULTS: Patients below four years of age mounted only weak and narrowly focused CD8+ T cell responses, and often maintained high CD4+ T cell counts in the face of high viral load. In contrast, patients four years and older had vigorous CD8+ T cell responses against a broader set of HIV antigens. Patients in this age group who maintained more than 400 CD4+ T cells/il displayed a strong positive correlation between HIV load and CD8+ T cell responses, while CD4+ T cell counts below 400 cells/il were associated with poor CD8+ T cell responses against HIV. Strikingly, two patients with extremely low CD4+ T cell counts displayed high levels of circulating dysfunctional Gag-specific CD8+ T cells. These Gag-specific CD8+ T cells displayed an activated, non-lymph node homing phenotype that was similar regardless of their ability to produce interferon-[gamma].

CONCLUSIONS: We have observed that young age is associated with very poor CD8+ T cell responses, and that stronger responses appear first at ages four years and older. Furthermore, our results are compatible with a model where HIV-specific CD8+ T cell immunity in the young immune system is antigen-driven and dependent on CD4+ T cell help.

Keywords: AEGIS, CD4 Lymphocyte Count, Viral Load, HIV, HIV Infections, Antigens, CD8, CD4-Positive T-Lymphocytes, HIV Seropositivity, HIV Antigens, HIV Long-Term Survivors, Interferon Type II, HLA-A2 Antigen, Adult, Child, Human, Infant, Infant, Newborn, immunology

020707
A10081