Preferential differentiation of pro-inflammatory CD4+ T cell

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					Preferential differentiation of pro-inflammatory CD4+ T cell phenotypes.
                                                                                                           Follicular
                                                                                                           dendritic
                                                                                                             cell
                                 Th0                                                                                Germinal
                                CD4+                                                                                 centre
    Myeloid                     T cell
    dendritic
      cell
                                                 T cell
                                                 zone        B cell




                                 TGF-β
                        IL-12     IL-6



                help
CD8+ cytotoxic
   T cell
                        Th1                         Th17
                       CD4+                         CD4+
                       T cell                       T cell
            INF-γ                        IL-17
                 Pro-inflammatory                                                                                   NEXT
                     response
Naive CD4+ T cells (Th0) interact with dendritic cells in the T cell zone of secondary lymphoid organs. Depending on the type
of cytokine stimulation by dendritic cells, Th0 T cells can differentiate into Th1, Th2, Th17 or Treg phenotypes. Th1 and Th17
T cells secrete INF-γ and IL-17, respectively, which promote pro-inflammatory immune responses. Conversely, Th2 and Treg
T cells secrete IL-10/IL-4 and IL-10, respectively, which antagonise pro-inflammatory immune responses by suppressing Th1
and Th17 T cell development. It is thought that IRIS may be due to an imbalance of pro-inflammatory and anti-inflammatory
immune responses during the immune reconstitution phase that occurs shortly after initiation of ARV therapy.
HIV induced CD4+ T cell sequestration in secondary lymphoid
tissue.                    Lymph
                                                            Afferent
                                                           lymphatic
                                                     node                                Follicular
                                                                                         dendritic                   vessel
                                                                                           cell

                                         Germinal
                                          centre




                                                                 Helper
                                                                 T cell


                                                          HIV
                                                 T cell
                                                 zone




                                                              Blood
                                                             vessels
                                      Efferent
                                     lymphatic
    PREVIOUS                           vessel                                                                       NEXT

Preferential replication of HIV in secondary lymphoid tissue results in accumulation of viral gp120,
which interacts with CD4 receptors expressed on CD4+ T cells. CD4 receptor stimulation promotes retention of CD4+ T cells
in the lymph node by interfererence with lymph node homing and exit receptor regulation. ARV therapy inhibits viral replication
and reverses the sequestration of CD4+ T cells. The first phase of immune reconstitution following ARV therapy is the
redistribution of sequestered CD4+ T cells from the lymph nodes to peripheral blood and tissues. It has been shown that the
majority of these cells are of a memory phenotype that may initiate uncontrolled pro-inflammatory immune responses to recall
antigens.
Pro-inflammatory immune response following redistribution of CD4+
T cells.
                                                                                               IRIS
                                                     Pathogen
                                                        Pro-inflammatory                      Tissue
                           Regional                                                         macrophage
                         lymph node                         response
                                                                           IL-17
                                                        INF-γ



                                                                  Th1              Th17
                   Redistribution                                CD4+              CD4+
                                                                 T cell            T cell

                                                                  Increased
                                                                    blood
                                               CD4               CD4+ T cells

                                TCR




               Memory
                CD4+
                T cell
    PREVIOUS                                                                                                          BACK

Soon after initiation of ARV therapy, a large reduction in levels in virus replication in lymphoid tissue leads to a reversal of
CD4+ T cell sequestration in lymph nodes resulting in their redistribution to peripheral blood and tissues. The majority of these
cells are of a memory phenotype that may initiate pro-inflammatory immune responses to recall antigens. In IRIS, it is thought
that Th1 and Th17 T cells responding to recall antigens derived from living/dead organisms or antigens in tissue may result
in uncontrolled inflammation due to an unbalanced anti-inflammatory response by Treg and Th2 T cells.

				
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posted:3/22/2011
language:English
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