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Abstract
HOST GENETIC AND IMMUNLOGIC RESPONSES MEDIATING LONG TERM SURVIVAL IN HIV-1-INFECTED AFRICAN CHILDREN
CHAKRABORTY R, SUTTON J, APPAY V, OTSYULA M, D'AGOSTINO A, ROWLAND-JONES S
AIMS: The magnitude, specificity and functional phenotype of HIV-1-specific CD8-T-Lymphocyte (CTL) and CD4 responses were studied among 49 HIV-1-infected African children. Comparisons were made between 14 Long Term Survivor Non-Progressors (LTSNPs - 1) and 19 Rapid/Typical Progressors (R/TPs - 3).
METHODS:a) HIV-1-specific CTLs were characterized by Elispot assay after molecular HLA typing. HIV-1 peptide specific CTLs were enumerated on the basis of gamma-interferon (gamma-IFN) release. b) CD8-depleted assays were used to detect CD4 mediated responses to a panel of HIV-1-specific and recall antigens. c) The functional phenotype of antigen specific CD8+ and CD4+ T cells were compared using HIV and/or CMV peptide HLA tetrameric complexes, and antibodies to perforin and gamma-IFN.
RESULTS: a) Group 1 had a greater number of HIV-1-specific CTL responses compared to group 3 (59/110 versus 67/175, p=0.01). Responses through 2 HLA class I alleles (B53 and Cw4) were associated with positive responses in group 1 (12/15 versus 2/12, p=0.001 and 4/6 versus 1/11, p=0.03, respectively. Responses through HLA B57/58 were seen more often in group 3 (2/12 versus 7/12, p=0.04). b) Group 1 had a greater number of CD4 responses (69/111 versus 13/67, p=10-7). Significant differences in responses were noted to CMV and p17 gag antigens (5/7 versus 0/4, p=0.04 and 7/7 versus 1/4, p=0.02, respectively. c) HIV-1-specific CTL elispot responses correlated in 8 children with tetramer staining. HIV-1-specific CTLs expressed low levels of perforin in all 8 donors. CMV-specific tetramer positive populations were identified in 5 children. The % of CD4+ cells to gag antigens (p17 and p24) and CMV producing gamma-IFN in a LTSNP was 1.22% and 1%, respectively.
CONCLUSIONS: 1) HIV-1-infected pediatric LTSNPs have a greater magnitude of HIV-1-specific CTL responses than R/TPs, particularly through HLA B53 and Cw4. 2) Non-progression is associated with strong HIV-specific lymphocyte responses.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
134
Suggested Citation
"CHAKRABORTYR, et al.
HOST GENETIC AND IMMUNLOGIC RESPONSES MEDIATING LONG TERM SURVIVAL IN HIV-1-INFECTED AFRICAN CHILDREN.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
134"
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