chapter  4
22 Pages

Consequences of HIV Infection on Thymus Function and T Cell Development

Introduction ......................................................................................................................................56 Overview ...................................................................................................................................56 T Cell Development in the Thymus .........................................................................................56

HIV Infection of Thymocyte Subsets..............................................................................................57 The Thymus as a Reservoir of HIV.........................................................................................57 Infection of Thymocytes...........................................................................................................57 Infection of Thymic Stromal Cells...........................................................................................58

Thymic Architecture ........................................................................................................................59 Thymic Histology .....................................................................................................................59 Thymic Pathology during HIV Infection .................................................................................59 The Aging Thymus ...................................................................................................................59

Early T Cell Ontogeny and Hematopoiesis.....................................................................................59 Thymopoiesis ............................................................................................................................59 Hematopoiesis ...........................................................................................................................60

Thymic Selection and T Cell Maturation........................................................................................60 Positive and Negative Selection ...............................................................................................60 Tolerance to HIV ......................................................................................................................60 Thymocyte Signaling and Death Mechanisms.........................................................................61

Thymic Microenvironment ..............................................................................................................63 Thymocyte-Stroma Cross Talk ................................................................................................63 Disruption of the Thymic Microenvironment ..........................................................................63 Indirect Effects of HIV on the Thymus ...................................................................................65

Thymic Output and T Cell Homeostasis .........................................................................................65 Attrition of T Cells ...................................................................................................................65 Thymic Output ..........................................................................................................................66 Peripheral Expansion ................................................................................................................67

Effects of Anti-HIV Therapy on the Thymus .................................................................................67 HAART .....................................................................................................................................67 Cytokines ..................................................................................................................................68

Summary ..........................................................................................................................................68 References ........................................................................................................................................68

Remarkable progress has been made over the last two and one-half decades in illuminating human immunodeficiency virus (HIV) pathology and disease progression to acquired immunodeficiency syndrome (AIDS). Accordingly, the broad spectrum of immune dysfunction characteristic of AIDS has been primarily attributed to depletion of CD4