4-1BB is expressed on CD45RAhiROhi transitional T cell in humans

Cell Immunol. 1996 Apr 10;169(1):91-8. doi: 10.1006/cimm.1996.0095.


Murine 4-1BB is an approximately 30-kDa glycoprotein expressed on activated T cells and plays a role in T-cell-mediated proliferative response. To date the majority of work on 4-1BB has been conducted in the mouse. To assess the role of 4-1BB in humans, mAbs were made against the recombinant human (rh) 4-1BB protein. One such mAb 4B4-1 specifically binds SF-21 insect cells expressing rh4-1BB but not irrelevant control protein as measured by flow cytometry (FCM). 4B4-1 mAb stains PMA- and ionomycin-stimulated CEM (human T lymphoma) cells and PHA-stimulated peripheral blood T cells, but not resting cells. 4B4-1 mAb immunoprecipitates both approximately 32 and approximately 80 kDa protein from rh4-1BB expressing SF-21 cells and an approximately 39- and approximately 85-kDa protein from PMA-stimulated CEM cells under reducing conditions by SDS-PAGE. As added proof of its specificity, binding of FITC-labeled 4B4-1 mAb to PHA-stimulated T cells was blocked by rh4-1BB protein. Together these data demonstrate that 4B4-1 is specific for 4-1BB in humans. Unlike in the mouse, 4-1BB is expressed much earlier (within 24 hr) peaking around 2-3 days following PHA stimulation. As in the mouse 4-1BB is induced on both CD4+ and CD8+ T cell subsets. 4-1BB expression is induced upon PHA stimulation in both the naive (CD45RAhi-CD45ROlo/-) and the memory (CD45RAlo/-ROhi) T cell populations. Virtually all CD45RAhiROlo/- cells upon culture in PHA give rise to an intermediate CD45RAhiROhi 4-1BB+ transitional cell and subsequently CD45RAlo/-ROhi 4-1BBlo/- and CD45RAlo/-ROhi 4-1BBhi cells. In contrast, approximately 27% of CD45RAlo/-ROhi 4-1BB- cells when cultured in PHA for 24 hr acquire 4-1BB expression and all remain CD45RAlo/-ROhi.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD
  • Cells, Cultured
  • Humans
  • Leukocyte Common Antigens / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Receptors, Nerve Growth Factor / biosynthesis*
  • Receptors, Nerve Growth Factor / immunology
  • Receptors, Tumor Necrosis Factor / biosynthesis*
  • Receptors, Tumor Necrosis Factor / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9


  • Antibodies, Monoclonal
  • Antigens, CD
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF9 protein, human
  • Tnfrsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Leukocyte Common Antigens