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Fibrotic Damage by HIV Limits Immune Reconstitution in Lymphatic Tissues in Gut

  Early in the course of HIV infection, collagen deposition in gut-associated lymphatic tissues (GALT) causes greater CD4+ T cell depletion than in other lymph tissues and limits the extent of immune reconstitution that can be achieved with antiretroviral medications, according to research by scientists at the University of Minnesota in Minneapolis and at the National Institutes of Health in Bethesda, Maryland.
  In the Journal of Infectious Diseases for August 15, Dr. Timothy W. Schacker and colleagues also present new evidence that earlier initiation of antiretroviral treatment than currently recommended "supports the greatest reconstitution of this population, as well as that of the peripheral blood and peripheral lymphatic tissues."
  Dr. Schacker, at the University of Minnesota, and colleagues obtained venous blood, inguinal lymph nodes, and biopsies of the terminal ileum GALT from HIV-infected individuals. At baseline, significant depletion of CD4+ T cells was observed in all compartments, particularly in gut lymphoid tissue. Even though circulating CD4+ T cells increased after 6 months treatment, the total population in lymphoid tissue remained unchanged.
  In patients with symptoms of acute HIV seroconversion, "the population of CD4+ Tcells in GALT and secondary lymph node tissue is already reduced by approximately 50%, compared with that in Peyer patches, lymph node tissue, or peripheral blood compartments," the researchers report.
  In these patients, early treatment leads to an increase in the central memory CD4+ cells population in Peyer patches.
  "The benefits of early treatment for immune reconstitution -- especially in the gut, the largest lymphoid organ of the immune system -- suggests to us that current recommendations to wait for a CD4+ T cell count of 350 cells/mm before initiation of ART may not be optimal for the restoration of immunity to the extent that may prove to be necessary for immunosurveillance against tumors and pathogens over a relatively normal life span," Dr. Schacker and colleagues conclude.
  They also speculate that early treatment with antifibrotic drugs might limit depletion and improve reconstitution.
  In a related editorial, Drs. Sarah W. Read and Irini Sereti, at the National Institute of Allergy and Infectious Diseases in Bethesda, add, "Therapeutic interventions directed at immune activation and fibrosis itself, such as interventions that inhibit transforming growth factor-beta signaling, should be investigated to determine whether collagen deposition can be prevented or reduced."
  J Infect Dis 2008;198:453-464.