Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro.
CD4(+)CD25(+) T cells have immunoregulatory and suppressive functions and are responsible for suppressing self-reactive cells and maintaining self-tolerance. In addition to CD4(+)CD25(+) T cells, there is some evidence that a fraction of CD4(+)CD25(-) T cells exhibit suppressive activity in vitro or in vivo. We have shown, using aged mice, that aging not only leads to a decline in the ability to mount CD4(+)CD25(-) T cell responses, but, at the same time, renders aged CD4(+)CD25(-) T cells suppressive. In this study we report two newly established mAbs that could abrogate the suppressive function of aged CD4(+)CD25(-) T cells. These mAbs recognized the same protein, the transmembrane phosphatase CD45. Cross-linking of CD45 on aged CD4(+)CD25(-) T cells was required for the disruption of their suppressive activity. Surprisingly, these mAbs also abrogated the suppressive action of CD4(+)CD25(+) T cells in vitro. Our results demonstrate an unexpected function of CD45 as a negative regulator neutralizing the suppressive activity of aged CD4(+)CD25(-) and young CD4(+)CD25(+) T cells.
Shimizu
Jun
J
Immunological Aging Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. jun@tmig.or.jp <jun@tmig.or.jp>
Iida
Ryuji
R
Sato
Yuji
Y
Moriizumi
Eiko
E
Nishikawa
Atsushi
A
Ishida
Yasumasa
Y
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000939:Epitopes; D006825:Hybridomas; D017493:Leukocyte Common Antigens / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens