Activated, Pro-Inflammatory Th1, Th17, and Memory CD4+ T Cells and B Cells Are Involved in Delayed-Type Hypersensitivity Arthritis (DTHA) Inflammation and Paw Swelling in Mice

Front Immunol. 2021 Aug 2:12:689057. doi: 10.3389/fimmu.2021.689057. eCollection 2021.


Delayed-type hypersensitivity arthritis (DTHA) is a recently established experimental model of rheumatoid arthritis (RA) in mice with pharmacological values. Despite an indispensable role of CD4+ T cells in inducing DTHA, a potential role for CD4+ T cell subsets is lacking. Here we have quantified CD4+ subsets during DTHA development and found that levels of activated, pro-inflammatory Th1, Th17, and memory CD4+ T cells in draining lymph nodes were increased with differential dynamic patterns after DTHA induction. Moreover, according to B-cell depletion experiments, it has been suggested that this cell type is not involved in DTHA. We show that DTHA is associated with increased levels of B cells in draining lymph nodes accompanied by increased levels of circulating IgG. Finally, using the anti-rheumatoid agents, methotrexate (MTX) and the anti-inflammatory drug dexamethasone (DEX), we show that MTX and DEX differentially suppressed DTHA-induced paw swelling and inflammation. The effects of MTX and DEX coincided with differential regulation of levels of Th1, Th17, and memory T cells as well as B cells. Our results implicate Th1, Th17, and memory T cells, together with activated B cells, to be involved and required for DTHA-induced paw swelling and inflammation.

Keywords: CD4+ T cell; DTHA mouse model; dexamethasone; methotrexate; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Antibodies / immunology
  • Arthritis, Experimental / immunology*
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Female
  • Foot
  • Hypersensitivity, Delayed / immunology*
  • Immunologic Memory
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Serum Albumin, Bovine / immunology
  • Spleen / immunology


  • Allergens
  • Antibodies
  • Serum Albumin, Bovine