1. Academic Validation
  2. Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis

Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis

  • J Immunol. 2003 Jul 15;171(2):576-83. doi: 10.4049/jimmunol.171.2.576.
Su K Seo 1 Hye Y Park Jae H Choi Won Y Kim Young H Kim Hyo W Jung Byungsuk Kwon Hyeon W Lee Byoung S Kwon
Affiliations

Affiliation

  • 1 Immunomodulation Research Center, University of Ulsan, Ulsan, Korea.
Abstract

Herpetic stromal keratitis (HSK) is a chronic inflammatory process in corneal stroma that results from recurrent HSV type 1 Infection. We used the murine model of HSK to demonstrate the importance of the interaction between an inducible T cell costimulatory receptor, 4-1BB, and its ligand, 4-1BB ligand (4-1BBL), in the development of this disease. In BALB/c mice, HSK ordinarily induced by Infection with the RE strain of herpes was prevented by blocking 4-1BB/4-1BBL interaction, either by deleting 4-1BB (in mutant 4-1BB(-/-) mice) or by introducing mAbs against 4-1BBL. The majority of T cells infiltrating the infected corneas were 4-1BB(+) activated effector cells that expressed cell surface markers CD44, CD25, and/or CD62L, as well as chemokine receptors CCR1, CCR2, and CCR5, and a limited number of TCR Vbeta chains (Vbeta8.1/8.2, Vbeta8.3, Vbeta10b, and Vbeta5.1/5.2, in order of abundance). Analysis of cell surface phenotypes showed that the failure to develop HSK in the 4-1BB(-/-) mice was associated with a reduced expression of CD62L at the time of T cell migration into the corneal stroma.

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