117. HIV-Specific CD8+ T Cells Are Present at a High Frequency in Breast Milk from HIV-Infected Women

Abstract

E-mail Abstract Author

Add To Itinerary

Session

Search Abstracts

Program

Session 26 Oral Abstract Session
Pediatric/Maternal-Fetal HIV Infection and Issues in HIV-Infected Women
Session Time: Wednesday, 10 am - 12:30 pm
Room 606-609

11:30 117.

HIV-Specific CD8+ T Cells Are Present at a High Frequency in Breast Milk from HIV-Infected Women
S. Sabbaj*, B. Edwards, M. Ghosh, K. Semrau, M. Mulligan, P. Goepfert, and G. Aldrovandi
Univ. of Alabama, Birmingham

Background: It is estimated that a third to half of infants in the developing world contract HIV via breast milk. However, most breast-fed infants avoid infection despite daily ingestion of massive amounts of HIV. Factors controlling HIV in breast milk are poorly understood. Since CTL responses have been shown to play a critical role in controlling HIV levels in the peripheral blood, our study sought to determine the presence of CD8+ T-cell responses in breast milk obtained from HIV-1-seropositive women.
Methods: Colostrum was obtained from HIV-seropositive and seronegative women. Cells were isolated by pelleting at 400 g x 15 minutes. BMC were stimulated with HIV-1 clade B peptides (20-mers overlapping by 10) spanning Gag, Pol, Nef, and Env. Responses to tetanus toxoid (TT), CMV, and PHA were used as positive controls. T-cell responses were enumerated by an IFN-gamma ELISPOT assay. CD8+ cell depletion and tetramer staining were used to assess the phenotype of the BMC in 1 volunteer.
Results: All volunteers had strong responses to PHA. All HIV-negative women (n=4) had detectable responses to CMV (range 113-700 SFC/million cells; mean = 358), but not to any of the HIV peptide pools. Conversely, all (n=5) HIV-infected women had responses to Gag peptide pools (range 240-1390 SFC/million cells; mean = 755), 4/5 to Pol, 3/5 to Nef, 2/5 to Env. In addition, 1/3 tested had detectable responses to TT and 2/3 had responses to CMV. Tetramer staining demonstrated 0.65% of cells present in breast milk obtained from an HIV-seropositive HLA-A3+ woman were CD8+/HLA-A3 Gag tetramer+. No HIV-specific tetramer positive cells were detected by tetramer in breast milk from an HLA-A3+ HIV-seronegative woman. Depletion studies demonstrated that CD8+ T cells mediated these responses.
Conclusions: This is the first study to demonstrate HIV-specific MHC class I restricted CD8+ T-cell responses to HIV antigens in breast milk obtained from all HIV-seropositive women tested. Moreover, these studies are the first to demonstrate antigen-specific CD8+ T-cell responses in human breast milk. Their presence suggests that they may play a role in limiting transmission and provide a rationale for vaccine studies enhancing these responses.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections