The regulatory function of umbilical cord blood CD4(+) CD25(+) T cells stimulated with anti-CD3/anti-CD28 and exogenous interleukin (IL)-2 or IL-15.
The abundance of CD4(+) CD25(+) regulatory T cells in umbilical cord blood (UCB) might contribute to the decreased severity of graft-vs.-host disease (GVHD) for UCB transplantation. This study aims to characterize the phenotypes and suppressive function of UCB CD4(+) CD25(+) T cells under the influence of anti-CD3/anti-CD28 (CD3/CD28) and exogenous interleukin (IL)-2 or IL-15. Higher percentages of CD4(+) CD25(high) and FoxP3(+) cells were detected in UCB compared to their adult counterparts. IL-15 was as effective as IL-2 in enhancing the proliferation of CD3/CD28 stimulated UCB CD4(+) CD25(+) T cells. Phenotypically, IL-2/IL-15-stimulated UCB CD4(+) CD25(+) T cells expressed higher level of CTLA-4, GITR, membrane bound transforming growth factor-beta (mTGF-beta), and especially Foxp-3 than controls. IL-2/IL-15-stimulated UCB CD4(+) CD25(+) T cells also produced much higher IL-10 and TGF-beta than controls; while IL-2/IL-15-stimulated UCB CD4(+) CD25(-) T cells showed increased TGF-beta, but not IL-10 production. IL-2/IL-15-cultured UCB CD4(+) CD25(+) T cells showed comparable suppressor activity on allogeneic adult CD4(+) T-cell proliferation compared to controls, partly through a contact-dependent fashion. Taken together, IL-2/IL-15-stimulated UCB CD4(+) CD25(+) T cells show distinct regulatory T-cell phenotypic and functional features, and may be applied for the alleviation of GVHD severity following UCB transplantation.
Lee
Chen-Cheng
CC
Department of Microbiology and Immunology, Graduate Institute of Basic Medical Science, Chang Gung University, Taoyuan, Taiwan.
Lin
Syh-Jae
SJ
Cheng
Po-Jen
PJ
Kuo
Ming-Ling
ML
D000906:Antibodies / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D019409:Interleukin-15 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019409:Interleukin-15; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit