부산대학교 도서관

HIV-1 infection is characterized by a progressive decline in [CD4.sup.+] T cells leading to a state of profound immunodeficiency. IL-2 therapy has been shown to improve [CD4.sup.+] counts beyond that observed with antiretroviral therapy. Recent phase III trials revealed that despite a sustained increase in [CD4.sup.+] counts, IL-2-treated patients did not experience a better clinical outcome [Abrams D, et al. (2009) N Engl J Med 361(16):1548-1559]. To explain these disappointing results, we have studied phenotypic, functional, and molecular characteristics of [CD4.sup.+] T cell populations in IL-2-treated patients. We found that the principal effect of long-term IL-2 therapy was the expansion of two distinct [CD4.sup.+][CD25.sup.+] T cell populations ([CD4.sup.+][CD25.sup.lo][CD127.sup.lo][FOXP3.sup.+] and [CD4.sup.+][CD25.sup.hi][CD127.sup.lo] [FOXP3.sup.hi]) that shared phenotypic markers of Treg but could be distinguished by the levels of CD25 and FOXP3 expression. IL-2-expanded [CD4.sup.+][CD25.sup.+] T cells suppressed proliferation of effector cells in vitro and had gene expression profiles similar to those of natural regulatory [CD4.sup.+][CD25.sup.hi][FOXP3.sup.+] T cells (Treg) from healthy donors, an immunosuppressive T cell subset critically important for the maintenance of self-tolerance. We propose that the sustained increase of the peripheral Treg pool in IL-2-treated HIV patients may account for the unexpected clinical observation that patients with the greatest expansion of [CD4.sup.+] T cells had a higher relative risk of clinical progression to AIDS. molecular profiling | immune-based therapy doi/ 10.1073/pnas.1000027107