CD4+ and CD8+ T lymphocyte regeneration after anti-retroviral therapy in HIV-1-infected children and adult patients

Abstract

Previous studies have shown a slow recovery of naive CD4+ T cell counts after anti-retroviral therapy in HIV-1-infected adults, which is in accordance with thymus atrophy after puberty. Here we investigate whether or not different patterns of naive CD4+ and CD8+ T cell repopulation are present in adult and child patients undergoing anti-retroviral treatment. Thus, 25 adults under highly active anti-retroviral therapy and 10 children under combined anti-retroviral therapy were retrospectively analysed for T cell subpopulations at baseline (T0) and around week 12 (T1) and week 24 (T2) of anti-retroviral treatment. Mean serum HIV-1 RNA levels dropped in both groups. Recovery of T cells in adults was characterized by a heterogeneous response between patients, with only 44% of them increasing their naive CD4+ and CD8+ T cell counts at T1, and changes in mean total CD4+ T cells were mainly shaped by memory cells. Otherwise, children were characterized by an early increase in naive T cells. Thus, at T1, all children analysed had a strong rise in CD4+ (from 389 +/- 116 to 569 +/- 121 cells/microl; P < 0.01), and nine out of 10 also in naive CD8+ T cells (from 244 +/- 58 to 473 +/- 85 cells/microl; P < 0.05). However, no significant correlation between age and naive repopulation was observed (P = 0. 22) in children. Thus, children had the earlier and greater increases in naive T cell subsets than adults, probably due to a more active thymus, with the potential for immune reconstitution when HIV-1 replication is controlled.

Fig. 1

Kinetics of CD4⁺ and CD8⁺ naive and memory lymphocyte subpopulations. The lines represent the pattern of absolute mean response on therapy in the T lymphocyte naive (N) and memory (M) subset, and the total T cell count (T), for: (a) CD4⁺ T cells in adults; (b) CD4⁺ T cells in children; (c) CD8⁺ T cells in adults; and (d) CD8⁺ T cells in children. Bars represent s.e.m. Note the axis break in (c).

Fig. 2

Change in patient’s T cell subsets after anti-retroviral treatment. Individual patient’s change in T cell subpopulation versus T₀ is shown for the naive CD4⁺ T cell subset at T₁ (a) and T₂ (b), and naive CD8⁺ T cell subset at T₁ (c) and T₂ (d) of anti-retroviral treatment. Patients were grouped into children (□) or adults (▪) and then identically arranged in all the plots, according to their naive CD4⁺ response at T₁. ND, Not determined.