CD4 AND CD8 T LYMPHOCYTES DURING HIV-INDUCED CHRONIC IMMUNE ACTIVATION

T cell proliferation occurs after cells receive appropriate antigenic and co-stimulatory signals; the strength and duration of antigen presentation are related to their commitment to clonal expansion and determine the response type (Th-1 or Th-2).¹⁸ The CD8 subset has a much lower activation threshold and produces a larger burst size than CD4.

Lack of complete immune recovery may, in part, be related to HIV-stimulated apoptosis or activation-induced cell death in T lymphocytes, which is reflected by changes in the distribution equilibrium of specific lymphocyte subsets.⁷ Gougeon et al., as early as 1996, demonstrated that lymphocyte populations from both healthy uninfected and HIV-1-infected patients undergo apop­tosis in vitro. However, the demographics of apoptotic CD4 from HIV-infected patients drastically change with the stage of disease.⁷ For example, in uninfected controls, CD4 make up 25% of the apoptotic population that decreases to 18% in asymptomatic patients and 4% during AIDS, whereas the CD8 subset represents a less variable but very large portion ranging from 37 to 45%.

The timing of treatment initiation also seems to influence the level of immune restoration. Hess et al. compared the maturation phenotype of immunodominant HIV-1-specific CD8 T cells in patients undergoing structured treatment interruptions during the acute phase of HIV-1 infection with untreated HIV-1 subjects for a 4-year period.²¹ Using the CD45RA (isoform of the CD45 molecule, which is characteristic of virgin/unprimed T lymphocytes) and CCR7 (a receptor for lymph tissue homing) markers to follow lineage differentiation, the authors found that patients exhibiting maxi­mum viral suppression during treatment interruption expanded fully differentiated effector CD8 T cells for various HLA class I tetramer accessible epitopes, whereas those exhibiting a lack of immune control had a paucity of fully differentiated CD8 T cells.²¹ In addition, Cossarizza et al. studied two treatment-naive populations (acutely infected and chronically infected treatment-naive populations). Of these two, only the acutely treated were able to restore T cell repertoire in both CD4 and CD8 subsets, whereas the latter group restored perturbations only in the CD8 subset repertoire.²² These results imply that HIV-1 generates apoptosis in CD4/CD8 subsets through different mechanisms. It is possible that the CD4 class may be subject to a global activation leading to generalized cell death whereas specific CD8 subsets are activated, expand, and progress to apoptosis, thus altering the composition of the total CD8 pool. The latter observation can be confirmed only by looking at the particular CD8 subclasses: naive, HIV-specific effector, central memory, and effector memory, which can be easily performed by using CD45RA and CCR7 markers and fluorescence-activated cell sorter (FACS) analysis.