TREC analysis shows little thymic damage in HIV-positive adolescents

A report published in the March issue of Clinical and Diagnostic Laboratory Immunology examined TREC values in a cohort of HIV positive adolescents.

T-cell receptor rearrangement circles (TREC) are DNA molecules that arise during T-cell development, and are present in cells that have recently emigrated from the thymus. During T-cell differentiation in the thymus gland, progenitor cells undergo T-cell receptor rearrangements. These result in the production of episomal DNA by-products called T-cell receptor rearrangement excision circles (TREC). Because TREC do not replicate with mitosis, they are diluted by cell division or lost with cell death. Recently developed tests allow TREC to be quantitated in peripheral blood mononuclear cells and in circulating CD4 cells specifically, as an estimate of thymic output.

The authors explain that “In cross sectional studies, the number of peripheral blood lymphocytes bearing TREC decreases with age, consistent with an anatomically demonstrated loss of thymic epithelial tissue. TREC numbers increase following haematopoietic stem cell transplantation and during therapy for human immunodeficiency virus (HIV) infection.” Therefore quantitation of TREC has been proposed as a parameter of thymic activity.

The investigators used real time polymerase chain reaction (PCR) to quantify TREC in blood samples from HIV-negative adolescents and found TREC values in blood T-cells very stable throughout adolescence ,which they explained was once believed to be a time of rapid involution of the thymus.

In addition, in cross sectional analysis they evaluated TREC values in a cohort of HIV-positive vertically infected adolescents and found evidence of ongoing thymopoiesis despite lifelong infection. The investigators conclude: “These data demonstrate the utility of TREC assessment in adolescents and that HIV infection does not uniformly result in accelerated thymic involution in childhood.”

Pham T, Belzer M, Church JA et al. Assessment of thymic activity in human immunodeficiency virus-negative and positive adolescents by real-time PCR quantitation of T-cell receptor rearrangement excision circles. Clin Diagn Lab Immunol 10(2): 323-8;March 2003

Comment

The reality is that TREC assessment is a useful research technique which provides optimistic evidence for continued immune reconstitution throughout childhood in response to HAART. TREC assays are not useful for clinical monitoring of individual children.

It would be interesting to know when TREC begin to decline to adult levels if they are stable throughout adolescence. Hopefully the investigators will continue to follow the HIV-uninfected adolescents they recruited.