Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection

Abstract

SUMMARYHIV-specific cytotoxic T lymphocytes (CTL) are thought to play a major role in viral control in HIV-infected adults. Changes in the relative proportions of CDS lymphocyte subpopulations are also thought to be associated with disease progression. Less is known about the relative effectiveness of CTL against different HIV targets, or about the relationship, if any. between CTL activity and CDS subpopuiations. We have measured CTL activity against four HIV gene products (gag. tat. pal and en\) and expression of CD45RO, CD45RA. HLA-DR, CD29. S6F1, and CD57 surface markers on CDS cells from nine HIV-infected and 11 HIV-uninfected children. Of nine HIV-infected children, six showed antigen-specific CTL activity on at least one occasion: 4/6 directed against tat, 6/6 against pol, 1/6 against env, and 1/6 against gag. However, the specificity of the CTL activity varied between children and within individual children with time. Furthermore, two uninfected children showed CTL activity, one to HW-gag. -pot and -tat. and the other to HW-pot. All the HIV-infected and two uninfected children had abnormal proportions of CDS subpopulations in whole blood compared with age-matched controls. There was no correlation between CTL activity and CDS subsets in whole blood. Five children changed from CTL-positive to CTL-negative (or vice versa) during the study. In these, the occasions when CTL activity was detected coincided with an increase in CDS cells, an expansion of HLA-DR^ CD8 cells and a loss of CD45RA ' CDS cells.

Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya

“…We found that 45% of infants were able to generate cellular immune responses of substantial breadth and magnitude; however, most responses were transient. Our finding confirms previous studies that detected responses in HIV-1 EU infants [22,27,28,31], and is consistent with our previous study that observed 47% prevalence of at least one positive ELISPOT assay using human leucocyte antigen (HLA)-matched peptide stimulation in breastfeeding EU infants [29]. We also found significant associations between maternal plasma and breastmilk HIV-1 viral levels and infant magnitude of HIV-1-specific ELISPOT responses, suggesting that antigen exposure modifies the induced infant HIV-1-specific immune responses.…”

“…HIV-1-specific cellular immune responses have been reported in varied HIV-1 EU populations, including commercial sex workers [15][16][17], HIV-1-discordant couples [18][19][20] and infants born to HIV-1-infected women [21][22][23]. CD4 1 and CD8 1 HIV-1-specific responses have been observed in EU infants, with prevalence ranging from 3 to 56% [24][25][26][27] and 0 to 47% [22,[27][28][29][30][31], respectively, resulting in controversy around the detection of these responses and their potential protective role. However, vaccine development relies upon understanding the induction of immune responses, and so it remains important to identify the correlates of presence and magnitude of HIV-1specific immune responses in EU individuals.…”

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

“…Previous studies by our group and others in perinatal HIV-exposed infants have reported evidence of HIV-specific immune response (4,(18)(19)(20)(21)(22)(23)(24)(25). HIV-specific immune response has also been observed in exposed noninfected adults (26)(27)(28)(29).…”

Peptide–MHC multimer-based monitoring of CD8 T-cells in HIV-1 infection and AIDS vaccine development

“…However, in the study by Betts et al, variations in the number of HIVspecific CD8 + T-cell in chronically infected patients were in much broader ranges -between 1.6 and 18.4% of total CD8 + T-cells [83]. HIV-1-specific CD8 + CTLs in HIV-1-infected children have frequency and specificity similar to those found in HIV-1-infected adults [84][85][86]. Frequencies of SIV-and HIV-1-specific T-cells are not the sole determinants of immunemediated protection in viral infection [83].…”