Gauduin MC, Liu C, Kaur A, Lifson J, Altman J, Johnson RP; Conference on Retroviruses and Opportunistic Infections.
7th Conf Retrovir Oppor Infect Jan 30 Feb 2 2000 Conf Retrovir Oppor Infect 7th 2000 San Franc Calif. 2000 Jan 30-Feb 2; 7: 184 (abstract no. 576).
Harvard Med. Sch., Southborough, MA.
CD4+ T-cell depletion and progression of HIV-1 disease are more rapid in infants and children than adults infected with HIV-1. Analysis of infant rhesus macaques infected with SIV has proven to be a valuable model for pediatric AIDS which allows for detailed analysis of the early immunologic events following acute lentivirus infection. In the present study we investigated SIV-specific cellular immune responses in 6 SIVmac239-infected newborn rhesus macaques, three of which expressed the MHC class I Mamu-A*01 allele. Animals were inoculated at day 1 or 2 after birth and were followed longitudinally at 1, 2, 3, and 4 weeks after infection, and then every 2 to 4 weeks thereafter. Monitoring of virologic and immunologic parameters at each time point included: quantitative assessment of proliferative responses to SIV p55 and gp160, four color flow cytometric analysis of circulating CD3+CD4+, CD3+CD8+ and CD3-CD8+ T lymphocytes, and SIV plasma viral RNA. Detection of SIV-specific CD8+ T cells was performed using Mamu-A*01 MHC tetramers complexed with the gag 11C-M peptide. The fraction of proliferating CD4+ and CD8+ lymphocytes was assessed using flow cytometric assessment of expression of the Ki67 antigen. In some animals, SIV-specific proliferative responses were 2 to 3-fold higher in the mesenteric LN or spleen as compared with peripheral blood. One to 3 weeks after SIV infection, we observed a 2 to 3-fold increase in proliferation of CD8+ T cells, peaking at up to 15% of CD8+ cells, a value that was 3 to 4-fold lower than observed in adult macaques. SIV-specific CD8+ cells identified using MHC tetramers peaked 3 to 4 weeks after SIV-infection, reaching a maximum of 1.0 to 2.6 % of all CD8+ T cells. The results suggest impaired expansion of CD8+ T cells in response to acute SIV infection may in part account for the more rapid disease progression in infants as compared with adults. However, the persistence of SIV-specific T helper responses even in infants with advanced SIV disease suggests institution of antiretroviral therapy may allow retention of virus-specific T helper responses in infected infants.
Publication Types:
Keywords:
- Adult
- Animals
- Antigens, CD3
- Antigens, CD4
- Antigens, CD8
- CD8-Positive T-Lymphocytes
- Child
- Gene Products, env
- Humans
- Infant
- Infant, Newborn
- Kinetics
- Lymphocyte Depletion
- Macaca
- Macaca mulatta
- RNA, Viral
- Simian immunodeficiency virus
- T-Lymphocytes
- immunology
Other ID:
UI: 102243452
From Meeting Abstracts