Temporary, but essential requirement of CD8+ T cells early in the pathogenesis of diabetes in BB rats as revealed by thymectomy and CD8 depletion.
Autoimmunity-prone BB rats demonstrate a T lymphocytopenia and abnormal T cell subset distribution. To test whether the life span of all T cells or only of certain subsets is reduced in BB rats, we thymectomised 8-week-old BB and PVG rats and subsequently assessed size and composition of the T cell population over a 6-week-period. In both strains, thymectomy (Tx) was followed by a decrease in peripheral T cell numbers, which was proportionally larger in BB rats. The decline of the Thy-1+ recent thymic migrant (RTM) T cell phenotype was similar in both strains. BB rats showed a rapid preferential loss of CD8+ and CD45RC+ T cells, whereas the relative loss of RT6+ T cells was proportional to that of all T cells and not significantly different from that in PVG rats. Tx at 8-week did not prevent diabetes. Tx of 4-week-old BB rats revealed essentially the same changes in peripheral T cell subset distribution as in 8-week-old animals. However, Tx at week 4 did prevent diabetes. Since this raised the possibility of a temporary requirement of CD8+ T cells for the development of diabetes, we performed CD8 depletions during different pre-diabetic intervals. We found that CD8 depletion from 4 to 8 and 4 to 14 weeks, but not from 8 to 14 weeks of age prevented diabetes. We conclude that the protective effect of early adult Tx is, at least in part, due to the rapid loss of CD8+ T cells, and that these cells are only required between 4 and 8 weeks of age for diabetes to develop in BB rats.
Groen
Herman
H
Department of Cell Biology, Immunology Section, Faculty of Medical Sciences, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Klatter
Flip
F
Pater
Jennie
J
Nieuwenhuis
Paul
P
Rozing
Jan
J
D000375:Aging / Q000502:physiology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003920:Diabetes Mellitus / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB; D018800:Thy-1 Antigens / Q000276:immunology; D013934:Thymectomy; D013997:Time Factors
D016827:CD8 Antigens; D018800:Thy-1 Antigens; D017493:Leukocyte Common Antigens