Lymphopenia-induced proliferation is a potent activator for CD4+ T cell-mediated autoimmune disease in the retina.
To study retinal immunity in a defined system, a CD4+ TCR transgenic mouse line (betagalTCR) specific for beta-galactosidase (betagal) was created and used with transgenic mice that expressed betagal in retinal photoreceptor cells (arrbetagal mice). Adoptive transfer of resting betagalTCR T cells, whether naive or Ag-experienced, into arrbetagal mice did not induce retinal autoimmune disease (experimental autoimmune uveoretinitis, EAU) and gave no evidence of Ag recognition. Generation of betagalTCR T cells in arrbetagal mice by use of bone marrow grafts, or double-transgenic mice, also gave no retinal disease or signs of Ag recognition. Arrbetagal mice were also resistant to EAU induction by adoptive transfer of in vitro-activated betagalTCR T cells, even though the T cells were pathogenic if the betagal was expressed elsewhere. In vitro manipulations to increase T cell pathogenicity before transfer did not result in EAU. The only strategy that induced a high frequency of severe EAU was transfer of naive, CD25-depleted, betagalTCR T cells into lymphopenic arrbetagal recipients, implicating regulatory T cells in the T cell inoculum, as well as in the recipients, in the resistance to EAU. Surprisingly, activation of the CD25-depleted betagalTCR T cells before transfer into the lymphopenic recipients reduced EAU. Taken together, the results suggest that endogenous regulatory mechanisms, as well as peripheral induction of regulatory T cells, play a role in the protection from EAU.
McPherson
Scott W
SW
Department of Ophthalmology, University of Minnesota, Minneapolis, MN 55455, USA. mcphe003@umn.edu
Heuss
Neal D
ND
Gregerson
Dale S
DS
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012173:Retinitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001616:beta-Galactosidase / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D001616:beta-Galactosidase