A new role for CD28 in the survival of autoreactive T cells in the periphery after chronic exposure to autoantigen.
Recent work demonstrates that costimulatory molecules play a critical role for clonal deletion of autoreactive T cells in the thymus. The role of CD28 in the survival of autoreactive T cells in the periphery, however, has not been reported. Here we demonstrate that while mutation of the CD28 gene consistently increased the burden of autoreactive T cells in the thymus, such an increase was not always found in the periphery, as the CD28(-/-) autoreactive T cells disappeared in the spleen over a period between 4 and 10 weeks. The disappearance of autoreactive T cells associates with a diminished induction of Bcl-2 protein by the self antigen and an increased proportion of apoptotic cells in the periphery. Moreover, the elimination of autoreactive T cells in the periphery requires chronic stimulation by the self antigen, as adoptive transfer analysis revealed no enhancement of apoptosis in CD28(-/-) T cells in antigen-bearing hosts over a 3 day period. Thus, CD28 plays a significant role in both clonal deletion and survival of autoreactive T cells after chronic exposure to autoantigens, resulting in opposite effects on the burden of autoreactive T cells.
Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA.
Jian-Xin
JX
Gao
Xing
X
Chang
Xincheng
X
Zheng
Jing
J
Wen
Lijie
L
Yin
Peishuang
P
Du
Pan
P
Zheng
Yang
Y
Liu
D000367:Age Factors; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology*; D017637:Clonal Deletion / Q000276:immunology*; D005434:Flow Cytometry; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology
D000951:Antigens, Neoplasm; D001324:Autoantigens; D018106:CD28 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; C076546:tumor rejection antigen P815A, mouse