AEGiS-13IAC: Characterization of a Rhesus Macaque infected with simian immunodeficiency virus that developed expansion of Ag-specific CD8+ T cells having specific defects in effector function.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Characterization of a Rhesus Macaque infected with simian immunodeficiency virus that developed expansion of Ag-specific CD8+ T cells having specific defects in effector function.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA106)

MacDonald KS, Xiong Y, Luscher MA, Ostrowski M, Li B
K.S. MacDonald, Department of Microbiology, Mount Sinai Hospital, 600 University Ave, Toronto, ON, M5G 1X5, Canada, Tel.: +1 416 586 8879, Fax: +1 416 586 8746, E-mail: kmacdonald@mtsinai.on.ca

BACKGROUND: To characterize a population of CD8+ T cells in acute SIVmac239 infection that bind MHC class I tetramer of Mamu A*01 complexed with the SIVmac gag CTL epitope p11c (CTPYDINQM) but do not respond in T cell functional assay.

METHODS: A rhesus macaque was acutely infected with SIVmac239 and cells were collected at 60 days post infection. Frozen splenocytes and PBMCs specific, for p11c in the context of MamuA*01 as measured by tetramer staining, were tested for the responses to the same antigen in functional assays including ELISpot and intracellular staining. Phenotypic analysis was performed using flow cytometry and different regimens were tested to restore responsiveness.

RESULTS: Visualization of p11c-specific CD8+ T cells by tetrameric staining showed significant levels of Ag-specific CD8+ T cells in both PBMC and spleen and the frequencies varied in different compartment (2.5% for spleen and 9.2% for PBMC). These CD8+ T cells, however, failed to produce cytokines in response to the p11c peptide although they responded to PMA plus ionomycin stimulation. CD8+ T cells specific for p11c expressed little Mamu LA-DR and CD69 but high CD28, suggesting that these SIV-specific CD8 T cells were differentiated but not activated. In addition, elevated levels of apoptosis were found in CD4+ T cells but not in CD8+ T cells indicating that apoptosis may not contribute to the unresponsiveness of CD8+ T cells. Deficiency of CD28 costimulation may not be involved in the induction of this unresponsiveness since anti-CD28 mAb did not restore T cell response. Long-term culture with IL-2 plus AZT restored p11c-specifc CD8+ T cell responses.

CONCLUSIONS: These results indicate that defects in CD8+ T cell responses can occur during an acute SIV infection. Further studies of the mechanism of this unresponsive state and its relationship to disease pathology are underway.

Keywords: AEGIS, SIV, Macaca mulatta, Antigens, CD8, CD8-Positive T-Lymphocytes, Antigens, CD28, Interleukin-2, Epitopes, Flow Cytometry, Peptides, Animal, Physiology, immunology
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MoOrA106