MARKERS OF IMMUNE ACTIVATION
Several studies have demonstrated an increase in CD38 and HLA-DR activation antigens on CD4 and CD8 cells in HIV-infected individuals.5,6 CD38 antigen is broadly distributed on both immature and activated lymphocytes, and its increased expression has been linked to poor prognosis of subjects with HIV disease.
The median density of CD38 molecules on CD4 and CD8 T cells is, in some studies, a more reliable measure of activated T cells than percentage of CD38 cells.20 The T cell activation in HIV is generalized, involving cells of antigen specificities other than HIV, as documented by CD38 upregulation in CD8 T cells specific for Epstein-Barr virus (EBV), cytomegalovirus, and influenza virus during primary HIV infection.3,4Although CD38 and DR are two markers that are used reliably to indicate immune activation, other markers that are indicative of ongoing immune activation include expression of HLA-DR and CD25 in CD4 T cells, CD57, and CD71 on CD8 T cells, and CD71 on B cells.8 Polyclonal hypergammaglobulinemia is another characteristic feature of HIV infection, which results from immune activation of B cells.21,22 CD4 T cells from HIV-1-infected patients express tumor necrosis factor (TNF)α, the TNF receptor (TNFR) ligand, and can polyclonally activate B cells.23 Levels of sCD8, sCD14, TNFα, neopterin, β2-microglobulin, sTNFR2, and sCD25 are also reported to be increased in serum of patients with progressive HIV infection.8
Cytokine dysregulation24,25 is a characteristic feature of HIV infection; excessive immune activation is associated with an increase of proinflammatory cytokines, interleukin (IL)-4, IL-5, IL-6, TNFα, and interferon (IFN) γ, and with a decline in IL-2 and IL-12. Increased lymphocyte apoptosis involving CD4 and CD8 T cells10,26,27 is regularly seen in HIV-infected individuals and reflects ongoing immune activation.