Abstract
BackgroundHIV-infected controllers control viral replication and maintain normal CD4+ T cell counts. Long Term Non-Progressors (LTNP) also maintain normal CD4+ T cell counts, but have on-going viral replication. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell counts in controllers and LTNP.Methods25 HIV-infected controllers and 14 LTNP were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Production and destruction of T cells were addressed by determination of T cell receptor excision circles (TREC), recent thymic emigrants, naïve cells, immune activation, senescence and apoptosis. Furthermore, telomere length was determined, and the amount of lymphoid tissue in tonsil biopsies was quantified.ResultsControllers presented with partly preserved thymic output, preserved expression of the IL-7 receptor and IL-7 receptor density, and lower levels of destruction of cells than progressors resembling HIV-negative healthy controls. In contrast, LTNP appeared much like progressors, and different from controllers in immune activation, senescence, and apoptosis. Interestingly, CD8+ RTE, TREC and telomere length were partly preserved. Finally, both controllers and LTNP displayed decreased amounts of lymphoid tissue compared to healthy controls.ConclusionsControllers presented with an immunological profile different from LTNP. While controllers resembled healthy controls, LTNP were similar to progressors, suggesting different immunological mechanisms to be responsible for preserved CD4+ T cell counts in LTNP and controllers. However, both controllers and LTNP presented with reduced amounts of lymphoid tissue despite preserved CD4+ T cell counts, indicating HIV to cause damage even in non-progressors.
Highlights
A minority of individuals infected with human immunodeficiency virus (HIV) do not progress to acquired immunodeficiency syndrome even in the absence of treatment
This study aimed to investigate production, destruction and distribution of T cells in HIV-infected controllers, Long Term NonProgressors (LTNP) and progressors in order to identify differences which could generate hypotheses for mechanisms leading to lack of disease progression in LTNP and controllers
We hypothesised that markers of increased production including T cell receptor excision circles (TREC) content, CD4 recent thymic emigrants (RTE), naive T cells and expression of the IL-7 receptor (IL-7R) on CD4+ T cells differed between progressors and non-progressors
Summary
A minority of individuals infected with human immunodeficiency virus (HIV) do not progress to acquired immunodeficiency syndrome even in the absence of treatment Some of these patients are able to control viral replication and maintain stable CD4+ T cell counts, and these patients are referred to as elite controllers (EC, ,50 copies/mL) or viremic controllers (VC, 50–2,000 copies/mL), respectively. The mechanism behind the lack of disease progression in LTNP is largely unknown Both LTNP and controllers are infected with replicant-competent virus [2] suggesting the host immune system to be involved in maintaining normal CD4+ T cell counts. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell counts in controllers and LTNP
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