Cutting edge: CD4-independent development of functional FoxP3+ regulatory T cells.
The CD4 coreceptor is mandatory for the differentiation and function of conventional MHC class II-restricted T cells, but little is known about its contribution in regulatory T cells (Tregs). We thus investigated the Treg compartment in mice lacking CD4. CD3+CD8-FoxP3+ cells were readily detected in the periphery of CD4(-/-) mice, where their percentages were even increased as compared with wild-type animals. These cells had a classical CD25+CD152+GITR+ Treg phenotype, were enriched in memory-type Tregs, and displayed a diversified TCR repertoire. Functionally, CD4(-/-) Tregs were equally as suppressive as CD4(+/+) Tregs in vitro as well as in vivo. Hence, the CD4 coreceptor is dispensable for the generation and function of FoxP3+ Tregs. Furthermore, CD3+CD8-FoxP3+ Tregs were also found to develop in the absence of both CD4 and MHC-II molecules, demonstrating that the generation of Tregs can occur independently of MHC-II recognition.
Blache
Céline
C
INSERM, Unité 905, Rouen, France; University of Rouen, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Institute for Biomedical Research, F-76000 Rouen, France.
Adriouch
Sahil
S
Calbo
Sébastien
S
Drouot
Laurent
L
Dulauroy
Sophie
S
Arnoult
Christophe
C
Le Corre
Stéphanie
S
Six
Adrien
A
Seman
Michel
M
Boyer
Olivier
O
D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D017252:CD3 Complex; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell