       Document 0372
 DOCN  M9610372
 TI    Interleukin 4 and T helper type 2 cells are required for development of
       experimental onchocercal keratitis (river blindness).
 DT    9601
 AU    Pearlman E; Lass JH; Bardenstein DS; Kopf M; Hazlett FE Jr; Diaconu E;
       Kazura JW; Department of Medicine, Case Western Reserve University,;
       Cleveland, Ohio 44106, USA.
 SO    J Exp Med. 1995 Oct 1;182(4):931-40. Unique Identifier : AIDSLINE
       MED/96018793
 AB    Inflammation of the corneal stroma (stromal keratitis) is a serious
       complication of infection with the nematode parasite Onchocerca
       volvulus. Because stromal keratitis is believed to be immunologically
       mediated in humans, we used a murine model to examine the role of T
       cells and T helper cell cytokines in the immunopathogenesis of these eye
       lesions. BALB/c mice immunized subcutaneously and injected
       intrastromally with soluble O. volvulus antigens (OvAg) developed
       pronounced corneal opacification and neovascularization. The corneal
       stroma was edematous and contained numerous eosinophils and mononuclear
       cells. Stromal keratitis in immunized mice was determined to be T cell
       dependent based on the following observations: (a) T cell-deficient nude
       mice immunized and injected intrastromally with OvAg fail to develop
       corneal pathology; and (b) adoptive transfer of spleen cells from
       OvAg-immunized BALB/c mice to naive nude mice before intrastromal
       injection of OvAg results in development of keratitis. OvAg-stimulated
       lymph node and spleen cell cytokine production was dependent on CD4
       cells and included interleukin (IL)-4 and IL-5, but not interferon
       gamma, indicating a predominant T helper type 2 cell-like response.
       Inflamed corneas from immunized BALB/c mice and from reconstituted nude
       mice had greatly elevated CD4 and IL-4 gene expression compared with
       interferon gamma. Mice in which the IL-4 gene was disrupted failed to
       develop corneal disease, demonstrating that IL-4 is essential in the
       immunopathogenesis of O. volvulus-mediated stromal keratitis.
 DE    Animal  Antigens, Helminth/IMMUNOLOGY  Base Sequence  Cornea/BLOOD
       SUPPLY/PATHOLOGY  Corneal Opacity  Female  Immunotherapy, Adoptive
       Interleukin-4/DEFICIENCY/GENETICS/*METABOLISM  Keratitis/CHEMICALLY
       INDUCED/*IMMUNOLOGY/PATHOLOGY  Mice  Mice, Inbred BALB C  Mice, Inbred
       C57BL  Mice, Nude  Molecular Sequence Data  Neovascularization,
       Pathologic/PATHOLOGY  Onchocerciasis, Ocular/*IMMUNOLOGY/PATHOLOGY
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Th2
       Cells/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

