|
|
||||||||
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114
Microglia share a lineage relationship with bone marrow-derived
monocytes/macrophages and dendritic cells, and their inclusion in
retinal and brain transplants may function as "passenger
leukocytes." In other solid allografts, passenger leukocytes are the
primary sources of immunogenicity, triggering alloimmune rejection. We
have conducted a series of in vitro and in vivo studies examining the
capacity of microglia cultured from forebrain to activate alloreactive
T cells and to induce and elicit alloimmunity. Cultured microglia
expressed class II MHC molecules and costimulatory molecules (B7-1,
B7-2, and CD40), and they secreted IL-12. Cultured microglia injected
s.c. into naive recipients induced allospecific delayed
hypersensitivity and elicited delayed hypersensitivity directed at
alloantigens. Cultured microglia differed from conventional APCs by
secreting significant amounts of mature TGF-ß2, but smaller amounts
of IL-12. Moreover, while both cultured microglia and conventional APC
stimulated T cell proliferation in vitro, microglia directed the
responding T cells toward the Th2 pathway in which IL-4, but not IL-2
and IFN-
, was secreted. The abilities of microglia to secrete
TGF-ß2, to stimulate alloreactive Th2 cells, and to induce anterior
chamber associated immune deviation when injected into the eye of naive
allogeneic mice suggest that they are not typical passenger leukocytes.
The unique functional properties of cultured microglia may account for
the capacity of neonatal retinal tissue transplanted into the eye to
alter the systemic alloimmune response in a manner that delays, but
does not prevent, graft rejection.
This article has been cited by other articles:
![]() |
N. D. Radtke, R. B. Aramant, M. J. Seiler, H. M. Petry, and D. Pidwell Vision Change After Sheet Transplant of Fetal Retina With Retinal Pigment Epithelium to a Patient With Retinitis Pigmentosa Arch Ophthalmol, August 1, 2004; 122(8): 1159 - 1165. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. P. M. Sutmuller, L. R. H. M. Schurmans, L. M. van Duivenvoorde, J. A. Tine, E. I. H. van der Voort, R. E. M. Toes, C. J. M. Melief, M. J. Jager, and R. Offringa Adoptive T Cell Immunotherapy of Human Uveal Melanoma Targeting gp100 J. Immunol., December 15, 2000; 165(12): 7308 - 7315. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Broderick, L. Duncan, N. Taylor, and A. D. Dick IFN-{gamma} and LPS-Mediated IL-10-Dependent Suppression of Retinal Microglial Activation Invest. Ophthalmol. Vis. Sci., August 1, 2000; 41(9): 2613 - 2622. [Abstract] [Full Text] |
||||
![]() |
G. Tezel, M. R. Hernandez, and M. B. Wax Immunostaining of Heat Shock Proteins in the Retina and Optic Nerve Head of Normal and Glaucomatous Eyes Arch Ophthalmol, April 1, 2000; 118(4): 511 - 518. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |