Greater thymic tissue associated with increased immunologic recovery

While treatment with highly active antiretroviral therapy (HAART) leads to some immunologic reconstitution, the origin of the “recovered” CD4+ cells is still not fully understood. Some recent studies have correlated size of thymic tissue with naive CD4+ cell increases during the early phase of treatment with HAART.

Further, the presence of a functional thymus that is capable of generating new naive T cells is also thought to lead to more significant normalization of the CD4+ repertoire. Still, the importance of a functional thymus for long-term immunologic reconstitution has yet to be clearly determined.

In a study published in The Journal of Infectious Diseases, investigators examined the impact of thymic size on immune recovery in HIV-infected patients. In the study, the thymus was visualized, using computed tomographic (CT) scans, in 25 HIV-infected patients who had received HAART for 6 to 18 months and had achieved viral loads <500 copies/mL.

In addition, 10 control subjects had CT scans for comparison. To determine thymic output, the number of CD4+ cells containing T cell receptor excision circles (TRECs) was measured.

The investigators found that a larger thymic size was significantly associated with higher CD4+ cell counts and higher CD4+ TREC frequency. In addition, based upon qualitative assessment of immunologic function in 19 patients, patients with greater thymic tissue appeared to have significantly broader immunologic repertoires, compared with patients with minimal thymic tissue.

The authors conclude, “we have demonstrated that, in adult HIV-infected patients receiving steady-state HAART, a relationship exists between thymic size (as measured by CT scan) and CD4+ cell counts and between thymic size and the percentage of newly produced CD4+ cells (expressed as the percentage ofCD4+ cells containing TRECs).

“Furthermore, a large thymus seems to be associated with a less perturbed CD4+ TCR repertoire. Together, these findings suggest that the adult thymus is functional to a certain degree and is involved in reconstituting the immune function in HIV-infected patients receiving steady-state HAART, generating new CD4+ cells that contain TRECs, and contributing to a broader immunologic repertoire.

“Developing strategies to increase residual thymic function may be beneficial for HIV-infected patients whose immune systems are not fully reconstituted during HAART.”