AEGiS-14IAC: Persistent cellular immune responses to cytomegalovirus (CMV) in HIV-1 infected African children.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Persistent cellular immune responses to cytomegalovirus (CMV) in HIV-1 infected African children.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10090)

Sutton JK, Appay V, Seneviratne S, Marchant A, Cross AM, Ogola S, Musoke R, D'Agostino A, Rowland-Jones SL, Chakraborty R
Oxford University, Oxford, United Kingdom

BACKGROUND: Both HIV-1 and CMV result in chronic infection and may induce strong cellular immune responses. CMV is implicated as a cofactor in the progression of HIV-1 disease, but the immune response to CMV itself in the context of HIV infection is not well characterised. Here we aimed to study the immune response to CMV in 26 perinatally HIV-1 infected antiretroviral naïve chlildren, in Nairobi, Kenya, classified according to CDC criteria.

METHODS: A combination of CD8 T cell-depleted Elispot assays and intracellular cytokine staining was used to screen responses to whole CMV viral lysate. In 9 children CMV-specific CD8 T cells were quantified by tetramer analysis. Urinary CMV antigenaemia (excretion) was quantified by PCR.

RESULTS: All 26 children were CMV seropositive and 8 donors excreted CMV antigen of which 4 were typical progressors (TPs). A CMV-specific CD4 or CD8 T cell response was detectable in 25/26 (96%) with 19 of these exhibiting both CD4 and CD8 responses. 3/12 and 2/12 TPs had undetectable CMV CD4 and CD8 responses respectively. The greatest magnitude of CD4 responses to CMV were observed in the 7 long term survivor non-progressors (LTSNPs) where the maximum frequencies of CD4 T cells specific for CMV as determined by intracellular staining for IFN-γ in two donors were 2.5% and 1.4%. All 7 LTSNPs exhibited ≥1% CD8 T cells specific for CMV. CD8 T cells specific for an HLA-A2 restricted CMV epitope were identified in 6/9 individuals by tetramer staining (maximum frequency 2.9% of CD8 T cells).

CONCLUSIONS: Cellular immune responses to CMV were detectable in the majority of HIV-1 infected children irrespective of HIV disease progression, though with stronger responses in LTSNPs. Using a whole virus antigen preparation, these data suggest that responses to viral pathogens other than HIV may be maintained for a period of time, even in the context of HIV disease progression.

Keywords: AEGIS, HIV-1, Cytomegalovirus, HIV Infections, Cytomegalovirus Infections, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, Antigens, Viral, Antigens, CD8, Antigens, CD4, HIV Long-Term Survivors, HIV, T-Lymphocytes, Cytotoxic, Anti-HIV Agents, T-Lymphocytes, HLA-A2 Antigen, T-Lymphocyte Subsets, Epitopes, Kenya, Child, Human, immunology

020707
A10090