Disrupted Homeostatic Cytokines Expression in Secondary Lymph Organs during HIV Infection

Int J Mol Sci. 2016 Mar 22;17(3):413. doi: 10.3390/ijms17030413.


Research has firmly established that infection by human immunodeficiency virus (HIV) leads to structural disruption in secondary lymph organs (SLOs) and that IL-7 expression by SLOs is downregulated in simian immunodeficiency virus (SIV)-infected rhesus macaques. However, the foregoing has not been demonstrated in HIV-infected patients. As well, SLO-produced chemokines and cytokines, other than IL-7, have not been tested. In this study, SLOs in HIV-infected patients exhibit decreased levels of lymphoid cytokines, such as IL-7 and C-C motif chemokine ligand 21 (CCL21), due to lower expression of lymphotoxin (LT)-β. Previous research has shown that LT-β is produced mainly by CD4⁺T cells in rhesus macaques, while our study found the same level of LT-β expressed by CD4⁺T and CD8⁺T cells in humans. CD8⁺T cells substitute for depleted CD4⁺T cells LT-β production. Only the total number of CD3⁺T cells can account for the majority of LT-β in human SLOs. This study indicates a possible mechanism and a potential target for improvement of SLO function in HIV-infected patients, a novel adjuvant therapy for AIDS.

Keywords: CCL21; IL-7; human immunodeficiency virus (HIV) infection; secondary lymph organs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Chemokine CCL21 / genetics
  • Chemokine CCL21 / metabolism*
  • Female
  • HIV Infections / metabolism*
  • Homeostasis
  • Humans
  • Interleukin-7 / genetics
  • Interleukin-7 / metabolism*
  • Lymph Nodes / metabolism*
  • Lymphotoxin-alpha / genetics
  • Lymphotoxin-alpha / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Spleen / metabolism*


  • Chemokine CCL21
  • Interleukin-7
  • Lymphotoxin-alpha