A synthetic mimetic of CD4 is able to suppress disease in a rodent model of immune colitis

Eur J Immunol. 1999 Jan;29(1):355-66. doi: 10.1002/(SICI)1521-4141(199901)29:01<355::AID-IMMU355>3.0.CO;2-G.


CD4+ mucosal T cells mediate the intestinal inflammation in Crohn's disease and may serve as an important target for immune intervention. Here we assessed the therapeutic effect of a synthetic mimetic of CD4 designed to mimic both the sequence and conformation of the complementarity-determining region 3 of murine CD4 V1 domain (rD-mPGPtide) in a mouse colitis model using immunization with 2,4,6-trinitrobenzene sulfonic acid (TNB). i.v. administration of the rD-mPGPtide but not control scrambled peptide could suppress severe inflammation in the chronic colitis mouse model. After treatment with the rD-mPGPtide, a striking improvement of diarrhea and acute wasting disease was observed with decreased mortality. Serum anti-TNB antibody titers, CD45RBlowCD4+ T cells in the lamina propria and IFN-gamma mRNA expression in the mucosa were significantly decreased with the rD-mPGPtide treatment. Anti-CD4 antibody also suppressed disease by depletion of CD45RBhighCD4+ T cells in the colonic mucosa. The observation that the synthetically engineered analogue of murine CD4 inhibits inflammation in a rodent disease model by different mechanisms than anti-CD4 antibody suggests that a human version of this peptide has potential therapeutic utility in CD4+ mucosal T cell-mediated intestinal inflammation in Crohn's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CD4 Antigens / chemistry
  • CD4 Antigens / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Crohn Disease / immunology
  • Crohn Disease / pathology
  • Crohn Disease / therapy*
  • Cytokines / genetics
  • DNA Primers / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Humans
  • Immunity, Mucosal / drug effects
  • Immunosuppressive Agents / therapeutic use*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred BALB C
  • Oligopeptides / therapeutic use*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / immunology


  • CD4 Antigens
  • Cytokines
  • DNA Primers
  • Immunosuppressive Agents
  • Oligopeptides
  • RNA, Messenger
  • reverse D amino acid mouse proline-glycine-proline peptide
  • trinitrophenyl-bovine serum albumin
  • Serum Albumin, Bovine