CD4+ T-Cell Cycling in HIV-Infected Patients with the Discordant Immunologic Response to the Antiretroviral Therapy

Abstract

Discordant immune response to antiretroviral therapy (ART) in HIV infection is characterized by insufficient reconstitution of peripheral CD4+ T lymphocyte numbers despite suppression of virus replication. The causes of inefficient regeneration of CD4+ T cells on ART remain elusive. The paper reports the study involving two groups of HIV-positive patients: patients with discordant response to ART (n = 20) and patients with standard response to therapy (n = 21). The numbers of cycling (Ki-67+), senescent (CD57+), and exhausted (PD-1+) CD4+ T lymphocytes of varying degree of maturity have been determined in peripheral blood and lymph nodes of HIV-positive individuals. CD4+ T cell division asymmetry index after in vitro stimulation has been analyzed. Histological study of the lymph nodes of HIV-infected patients was carried out. It has been demonstrated that in the individuals with discordant immune response to ART, intensive CD4+ T cell cycling does not result in the increase in their count neither in peripheral blood, nor in the secondary lymphoid organs. At the same time, in the patients with impaired immune system recovery, increased cell proliferation is followed by the accumulation of exhausted CD4+ T lymphocytes. Moreover, patients with discordant immune response to ART revealed an asymmetric division of in vitro stimulated CD4+ T cells. The observed defects may be the cause of inefficient immune system recovery in HIV-infected patients on ART.