Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Circulating FOXP3 CTLA-4 CD25 Regulatory T Cells in Human Infants Counteract the Maturation and Homing Receptor Switch of CD4 T Cells at 18 and 36 Months of Age.

Rabe2,  Hardis, Lundell2,  Anna-Carin, Andersson2,  Kerstin, Adlerberth1,  Ingegerd, Wold1,  Agnes E., Rudin3,  Anna

Dept of Clinical Bacteriology
Dept of Rheumatology and Inflammation Research
Dept of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

Background:

FOXP3+ CTLA-4+ CD25+ regulatory T cells are essential to prevent general overactivation of T cells and ensuing autoimmune and inflammatory disease as the lack of these cells leads to a lethal inflammatory syndrome. However, it is not known if the numbers of these cells in the circulation in early infancy of healthy children are associated with lower levels of activation and maturation of the T cells at later ages.

Methods:

We followed a cohort of 66 children prospectively from birth to 3 years of age and analyzed T cells in blood samples phenotypically and quantitatively from ages 0 and 4 days, 1, 4 and 18 months and 3 years of age. The analysis of the CD4+ T cells was performed using flow cytometry to investigate the relation of the numbers of regulatory T cells in the circulation to the maturation and homing receptor switch of the CD4+ T cells at older ages. The relationship was analyzed using multivariate analysis by principal component analysis (PCA), orthogonal partial least squares modeling (OPLS) and thereafter univariate analyses as appropriate.

Results:

We analyzed the numbers of regulatory T cells using both FOXP3 and CTLA-4 as markers together with CD25. We showed that the T cells expressing FOXP3 and CTLA-4, respectively, were associated in PCA and OPLS at 4, 18 and 36 months of age but not at earlier ages. The numbers of regulatory T cells av 4 and 18 month of age were positively associated with the proportion of immature unactivated CD45RA+ T cells as well as with gut-homing a4b7+ CD4+ T cells at 18 and 36 months of age. Conversely, the numbers of regulatory T cells were negatively associated with the proportion of mature and previously activated CD45RO+ T cells as well as with CD4+ T cells expressing the extraintestinal homing marker CCR4.

Conclusion:

We show for the first time that higher numbers of circulating FOXP3+ CTLA-4+ regulatory T cells in healthy infants are strongly related to a lower proportion of mature previously activated CD4+ T cells at later ages. We conclude that the number of regulatory T cells in the circulation is important in the function of inhibition of immune activation, probably both to endgenous and exogenous antigens. Therefore, lower numbers of regulatory T cells in the circulation might preceed the onset of inflammatory disease.

To cite this abstract, please use the following information:
Rabe, Hardis, Lundell, Anna-Carin, Andersson, Kerstin, Adlerberth, Ingegerd, Wold, Agnes E., Rudin, Anna; Circulating FOXP3 CTLA-4 CD25 Regulatory T Cells in Human Infants Counteract the Maturation and Homing Receptor Switch of CD4 T Cells at 18 and 36 Months of Age. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1248
DOI: 10.1002/art.29014

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