Comprehensive screening reveals strong and broadly directed human immunodeficiency virus type 1-specific CD8 responses in perinatally infected children

被引:31
作者
Feeney, ME
Roosevelt, KA
Tang, Y
Pfafferott, KJ
McIntosh, K
Burchett, SK
Mao, C
Walker, BD
Goulder, PJR
机构
[1] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA
[3] Harvard Med Sch, Boston, MA USA
[4] Childrens Hosp, Boston, MA 02115 USA
[5] John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England
关键词
D O I
10.1128/JVI.77.13.7492-7501.2003
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Advances in antiviral therapy have dramatically shifted the demographics of pediatric human immunodeficiency virus type 1 (HIV-1) infection in the developed world, and a growing proportion of perinatally HIV-1-infected children are now entering their second or even third decade of life. Although cellular immune responses to HIV are known to be weak in early infancy, the magnitude, breadth, and specificity of responses later in childhood have not been characterized in detail. We performed a comprehensive characterization of HIV4-specific CD8 responses in 18 perinatally infected children (age range, 6 to 17 years), most of whom were on antiviral therapy, using both, previously defined HIV-1 epitopes and overlapping peptides spanning all HIV-1 proteins. Multispecific responses were detected in all subjects and accounted for a median of 0.25 to 0.3% of all peripheral blood mononuclear cells that was similar to the magnitude seen in HIV-infected adults. CD8 responses were broadly directed at an average of 11 epitopes (range, 2 to 27 epitopes) and targeted nearly all HIV-1 proteins, with the, highest proportion in Gag. Responses were readily detected even in those children with suppressed viremia on highly active antiretroviral therapy, although the breadth (P = 0.037) and the magnitude (P = 6.021) were significantly lower in these subjects. Each child recognized only a small minority of the HIV-1 optimal epitopes defined for his or her class I HLA alleles. Together, these data indicate that perinatally infected children who survive infancy mount a robust HIV-1-specific CD8 response that is much stronger than previously thought and is comparable in magnitude and breadth to that of adults. Moreover, this response has the-potential to be broadened to target more epitopes, making these children attractive candidates for immunotherapeutic interventions.
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页码:7492 / 7501
页数:10
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