CD4+ T Cell Depletion, Immune Activation and Increased Production of Regulatory T Cells in the Thymus of HIV-Infected Individuals

Abstract

Mechanisms by which HIV affects the thymus are multiple and only partially known, and the role of thymic dysfunction in HIV/AIDS immunopathogenesis remains poorly understood. To evaluate the effects of HIV infection on intra-thymic precursors of T cells in HIV-infected adults, we conducted a detailed immunophenotypic study of thymic tissue isolated from 7 HIV-infected and 10 HIV-negative adults who were to undergo heart surgery. We found that thymuses of HIV-infected individuals were characterized by a relative depletion of CD4+ single positive T cells and a corresponding enrichment of CD8+ single positive T cells. In addition, thymocytes derived from HIV-infected subjects showed increased levels of activated and proliferating cells. Our analysis also revealed a decreased expression of interleukin-7 receptor in early thymocytes from HIV-infected individuals, along with an increase in this same expression in mature double- and single-positive cells. Frequency of regulatory T cells (CD25+FoxP3+) was significantly increased in HIV-infected thymuses, particularly in priorly-committed CD4 single positive cells. Our data suggest that HIV infection is associated with a complex set of changes in the immunophenotype of thymocytes, including a reduction of intrathymic CD4+ T cell precursors, increased expression of activation markers, changes in the expression pattern of IL-7R and enrichment of T regulatory cells generation.

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

“…Enhanced generation of nTreg cells from the thymus,269 increased iTreg induction in the periphery,270, 271 and enhanced CD4 + Treg cell survival272 have all been suggested to contribute to this increase. Furthermore, as HIV‐specific Tregs are induced during infection,273, 274 the increase in CD4 + Treg frequencies may be, in part, driven by antigenic stimulation.…”

Effect of Highly Active Antiretroviral Therapy on T-Cell Sub-population Profile in Human Immunodeficiency Virus-1 Infected Patients

“…Frequency of regulatory T cells (CD25 + FoxP3 + ) was increased in HIV-infection and with aging [63], particularly in priory-committed CD4 + single positive cells. On the other hand data suggest that HIV infection is associated with a complex set of changes in the immunophenotype of thymocytes, including a reduction of intrathymic CD4 + T cell precursors, increased expression of activation markers, changes in the expression pattern of IL-7R and enrichment of T regulatory cells generation [27,95] [96,97]. Whereas, the study conducted in Uganda show, T-reg number is strongly correlated with both CD4 + and CD8 + T cell activation.…”

“…This subset of T cells is defined phenotypically by the presence on its surface of the CD4 + molecule, which serves as the primary cellular receptor for HIV. A co-receptor must also be present together with CD4 + molecules for efficient fusion and entry of HIV-1 into its target cells [26,27]. Highly active antiretroviral therapy (HAART), two or more nucleoside analogues (NRTIs) in combination with at least one protease inhibitors (PI) or one non-nucleoside reverse transcriptase inhibitors( NNRTI); one NRTI in combination with at least one PI and at least one NNRTI; tenofovir containing regimen of three or more NRTIs in the absence of both PIs and NNRTIs classified as HAART [28]; greatly decreases plasma HIV-1 viral RNA concentrations and increases CD4 + T cell counts even in patients at advanced stages of the disease [29][30][31].…”

Oxidants and Antioxidants in the Pathogenesis of HIV/AIDS

“…However, when T-lymphocytes become infected, their elimination results in a weakened immune function at a time in which the body needs it most. The body is faced with a dilemma of promoting apoptosis to eliminate HIV, yet consequently lowering the body's resistance to HIV [24].…”