CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I-alphabetaTCR interaction and become IL-10-producing active regulatory cells.
CD8(+)CD122(+) regulatory T cells (CD8(+)CD122(+) Treg) are naturally occurring Treg that effectively suppress the proliferation and IFN-gamma production of both CD8(+) and CD4(+) target cells. This study investigated the molecular mechanisms of the recognition of target cells by CD8(+)CD122(+) Treg using an in vitro culture system that reconstitutes the regulatory action of these cells. Naive CD8(+)CD122(+) Treg co-cultured with pre-activated T cells became active Treg that produced IL-10 and suppressed IFN-gamma production from the target T cells. CD8(+)CD122(+) Treg effectively suppressed the IFN-gamma production of the target cells of syngeneic mouse strains but not of allogeneic mouse strains with incompatible MHC. By using MHC-congeneic mouse strains, MHC-restricted suppression by CD8(+)CD122(+) Treg was further confirmed. The blockade of cell surface molecules either on the Treg or on the target cells by specific blocking antibodies indicated that H-2K, H-2D, alphabetaTCR and CD8 were involved in the regulatory action but I-A and Qa-1 were not. These results indicate that CD8(+)CD122(+) Treg recognize already-activated T cells via the interaction of conventional MHC class I-alphabetaTCR and become active regulatory cells that produce IL-10 and suppress the target cells.
Rifa'i
Muhaimin
M
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Shi
Zhe
Z
Zhang
Shu-Yun
SY
Lee
Young Ho
YH
Shiku
Hiroshi
H
Isobe
Ken-Ichi
K
Suzuki
Haruhiko
H
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D015194:Diffusion Chambers, Culture; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D018189:Immunomagnetic Separation; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D037182:T-Cell Antigen Receptor Specificity
D015395:Histocompatibility Antigens Class I; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; D007371:Interferon-gamma