Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO.
Although human naturally occurring regulatory T cells (Tregs) may express either CD45RA or CD45RO, we find in agreement with previous reports that the ( approximately 80%) majority of natural Tregs in adults are CD45RO(+). The proportion of CD45RA(+) Tregs decreases, whereas CD45RO(+) Tregs increase significantly with age. Nevertheless, a small proportion of CD45RA(+) Tregs are found even in old (>80 y) adults and a proportion of these express CD31, a marker for recent thymic emigrants. We found that CD45RO(+) Tregs were highly proliferative compared with their CD45RA(+) counterparts. This was due in part to the conversion of CD45RA Tregs to CD45RO expression after activation. Another difference between these two Treg populations was their preferential migration to different tissues in vivo. Whereas CD45RA(+) Tregs were preferentially located in the bone marrow, associated with increased CXCR4 expression, CD45RO(+) Tregs were preferentially located in the skin, and this was associated with their increased expression of CLA and CCR4. Our studies therefore show that proliferation features strongly in maintenance of the adult Treg pool in humans and that the thymus may make a minor contribution to the maintenance of the peripheral pool of these cells, even in older adults. Furthermore, the different tissue compartmentalization of these cells suggests that different Treg niches exist in vivo, which may have important roles for their maturation and function.
Division of Infection and Immunity, Department of Immunology, University College London, London W1T 4JF, United Kingdom.
Nicola J
NJ
Booth
Arthur J
AJ
McQuaid
Toni
T
Sobande
Steve
S
Kissane
Elaine
E
Agius
Sarah E
SE
Jackson
Mike
M
Salmon
Francesco
F
Falciani
Kwee
K
Yong
Malcolm H
MH
Rustin
Arne N
AN
Akbar
Milica
M
Vukmanovic-Stejic
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009928:Organ Specificity / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007527:Isoenzymes; D017493:Leukocyte Common Antigens