IL-7 drives Th1 and Th17 cytokine production in patients with primary SS despite an increase in CD4 T cells lacking the IL-7Rα.
OBJECTIVE
To study the phenotypic characteristics of and the balance between systemic IL-7 receptor (IL-7R)α+ and IL-7Rα- Tregs in primary SS (pSS) patients as compared with control subjects and to assess the functional consequences this has for (IL-7-induced) T-cell activation.


METHODS
The functional properties of IL-7Rα+ and IL-7Rα- (CD25+) CD4 T cells from pSS patients were tested in vitro. Expression of CD25 and FoxP3 by IL-7Rα+ and IL-7Rα- CD4 T cells from pSS patients and healthy controls (HCs) were assessed. Also, the net ex vivo T-cell cytokine production and the capacity of IL-7 to activate total CD4 T cells from pSS patients compared with HCs in vitro was tested.


RESULTS
IL-7Rα+ T cells from pSS patients strongly proliferated and their numbers were slightly reduced compared with HCs. This reduced number was caused by an increase in both anergic and suppressive IL-7Rα- CD25+ T cells expressing high levels of FoxP3, but also by increases in IL-7Rα- CD25- CD4 T cells that only moderately expressed FoxP3. This altered balance in IL-7Rα+ and IL-7Rα- CD4 T cells was accompanied by unchanged ex vivo Th1, Th2 and Th17 cytokine production of total CD4 T cells. Furthermore, the increased numbers of IL-7Rα- CD25+ T cells did not prevent specific IL-7-induced Th1 and Th17 cytokine production by IL-7Rα+ T cells.


CONCLUSIONS
IL-7Rα+ cells are highly proliferating cells that respond strongly to IL-7 despite an increased number of IL-7Rα- T cells that express FoxP3 and CD25. The recent finding that IL-7 and IL-7Rα+ T cells were both found to be increased in exocrine glands of pSS patients indicates that IL-7 could contribute to glandular inflammation by activation of IL-7Rα+ responder T cells despite the increased numbers of Tregs.
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
Angela
A
Bikker
Fréderique M
FM
Moret
Aike A
AA
Kruize
Johannes W J
JW
Bijlsma
Floris P J G
FP
Lafeber
Joël A G
JA
van Roon
D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D005088:Exocrine Glands / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D061251:Primary Cell Culture; D020395:Receptors, Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508717:IL17A protein, human; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain