CD8+CD28- regulatory T lymphocytes prevent experimental inflammatory bowel disease in mice.
OBJECTIVE
Immune responses to innocuous intestinal antigens appear tightly controlled by regulatory T lymphocytes. While CD4+ T lymphocytes have recently attracted the most attention, CD8+ regulatory T-cell populations are also believed to play an important role in control of mucosal immunity. However, CD8+ regulatory T-cell function has mainly been studied in vitro and no direct in vivo evidence exists that they can control mucosal immune responses. We investigated the capacity of CD8+CD28- T cells to prevent experimental inflammatory bowel disease (IBD) in mice.


METHODS
CD8+CD28- regulatory T cells were isolated from unmanipulated mice and tested for their capacity to inhibit T-cell activation in allogeneic mixed lymphocyte cultures in vitro and to prevent IBD induced by injection of CD4+CD45RB(high) cells into syngeneic immunodeficient RAG-2 mutant mice.


RESULTS
CD8+CD28- T lymphocytes inhibited proliferation and interferon gamma production by CD4+ responder T cells in vitro. CD8+CD28- regulatory T cells freshly isolated from spleen or gut efficiently prevented IBD induced by transfer of colitogenic T cells into immunodeficient hosts. Regulatory CD8+CD28- T cells incapable of producing interleukin-10 did not prevent colitis. Moreover, IBD induced with colitogenic T cells incapable of responding to transforming growth factor beta could not be prevented with CD8+CD28- regulatory T cells. CD8+CD28+ T cells did not inhibit in vitro or in vivo immune responses.


CONCLUSIONS
Our findings show that naturally occurring CD8+CD28- regulatory T lymphocytes can prevent experimental IBD in mice and suggest that these cells may play an important role in control of mucosal immunity.
Ménager-Marcq
Ingrid
I
Centre de Physiopathologie de Toulouse Purpan, INSERM Unité 563, Toulouse, France.
Pomié
Céline
C
Romagnoli
Paola
P
van Meerwijk
Joost P M
JP
D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy / Q000379:methods; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D018106:CD28 Antigens; D016827:CD8 Antigens; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma