Intestinal double-positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines

Eur J Immunol. 2006 Mar;36(3):583-92. doi: 10.1002/eji.200535520.


Peripheral blood and intestinal CD4+CD8+ double-positive (DP) T cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single-positive T cells. Intestinal DP T cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T cells populations compared to CD4+ single-positive T cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytokines / immunology*
  • Cytokines / metabolism
  • HIV / immunology
  • HIV Infections / immunology
  • HLA-DR Antigens / immunology
  • Immunity, Mucosal / immunology*
  • Immunologic Memory / immunology*
  • Intestines / cytology
  • Intestines / immunology*
  • Lymphocyte Activation
  • Macaca mulatta
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology
  • Mucous Membrane / metabolism
  • Organ Specificity / immunology
  • Receptors, CCR5 / immunology
  • Simian Immunodeficiency Virus / immunology
  • Virus Replication / immunology


  • Antigens, CD
  • Cytokines
  • HLA-DR Antigens
  • Receptors, CCR5