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, 181 (1), 110-7

The Influence of Paediatric HIV Infection on Circulating B Cell Subsets and CXCR5(+) T Helper Cells

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The Influence of Paediatric HIV Infection on Circulating B Cell Subsets and CXCR5(+) T Helper Cells

A Bamford et al. Clin Exp Immunol.

Abstract

Antiretroviral therapy (ART) only partially restores HIV-induced alterations in lymphocyte populations. We assessed B and T cell phenotypes in a cohort of children from a single centre in the United Kingdom with perinatally acquired HIV compared to healthy controls. The majority of HIV infected children (44 of 56) were on fully suppressive combination ART. Children with perinatally acquired HIV had significantly lower memory B and CD4(+) CD45RO(+) CXCR5(+) [follicular T helper cell (Tfh)-like] T cell percentages. Detectable viraemia was associated with higher CD21(-) (activated and exhausted/tissue-like memory) B cells. A greater proportion of life spent on suppressive ART was associated with higher memory B cell percentages. These results suggest that early and sustained suppressive ART may preserve B and T cell phenotypes in perinatally acquired HIV and limit deficits in humoral immunity. A lower proportion of circulating Tfh-like cells in HIV infected children appears to be independent of HIV treatment history and ongoing HIV viraemia and warrants further investigation.

Keywords: B cell; HIV; follicular T helper; memory; paediatric.

Figures

Figure 1
Figure 1
Gating strategy for identification of (a) B cell subsets and (b) T cell subsets. Following identification of live CD3 cells, CD19+ B lymphocytes were identified by sequentially gating forward‐scatter (FSC)‐A versus side‐scatter (SSC)‐A, FSC‐A versus FSC‐H, CD19 versus SSC‐A. CD10+CD27 and CD27++ immunoglobulin (Ig)D cells were then quantified. The remaining cells were subdivided in two ways: CD27 versus IgD and CD27 versus CD21, resulting in eight further subsets. Following identification of live CD19CD14 cells, CD4+ T lymphocytes were identified by sequentially gating FSC‐A versus SSC‐A, FSC‐A versus FSC‐H, CD3 versus CD4. Further subsets were identified using CD45RO, CXCR5 and inducible T cell co‐stimulator (ICOS). Typical contour plots from (c) a healthy child and a child with perinatally acquired HIV of approximately the same age, (d) a child with detectable viral load (VL) and a child with VL < 50 copies/ml. Children with perinatally acquired HIV have higher percentages of naive B cell subsets (CD27) and a correspondingly lower percentage of memory subsets (CD27+) compared to healthy children. Detectable VL is associated with an over‐representation of CD21 populations (CD27+CD21 and CD27CD21). (e) Regression plots comparing healthy children with children with perinatally acquired HIV. Subsets are reported as described for Table 1. When comparing HIV with HIV+ groups, significant differences in CD27+CD21+, CD27IgD+, CD27+IgDv, CD27+IgD and CD45RO+CXCR5+ cells were observed after adjusting for age (P < 0·05) HIV− = HIV uninfected child healthy control; HIV+ = HIV‐infected child; VL= HIV viral load; ln = natural log.

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