Effect of interleukin-15 on effector and regulatory function of anti-CD3/anti-CD28-stimulated CD4(+) T cells.
Autologous transfer of anti-CD3/anti-CD28 (CD3/CD28)-activated CD4(+) T cells may benefit patients receiving autologous stem cell transplant with severe CD4 lymphopenia. Interleukin (IL)-15, an IL-2-like cytokine that promotes T cell survival may enhance immune reconstitution in conjunction with adoptive immunotherapy. We investigated the effect of IL-15 on effector and regulatory function of CD3/CD28-activated CD4(+) T cells. IL-15 upregulated CD45RO and CD25 whereas it down regulated CD62L expression of CD3/CD28-stimulated CD4(+) T cells. Both type 1 (IFN-gamma, tumor necrosis factor (TNF)-alpha) and type 2 (IL-5 and IL-10) production by CD3/CD28-activated CD4(+) T cells was further enhanced by IL-15. Co-culture experiments revealed that CD3/CD28-activated CD4(+) T cells down regulated proliferation of autologous peripheral blood lymphocytes (PBLs) and CD8(+) PBL subsets upon TCR ligation, a contact-dependent effect that was further enhanced by pretreatment with IL-15. Flow cytometric analysis of cell mixture with carboxyfluorescein diacetate succinimidyl ester and Annexin-V-PE staining revealed that CD3/CD28+IL-15-activated CD4(+) T cells showed increased apoptosis over CD4(+) T cells stimulated with CD3/CD28 alone. Taken together, pretreatment of CD3/CD28-activated CD4(+) T cells with IL-15 may increase regulatory function but may aggravate activation-induced apoptosis of CD3/CD28 CD4(+) T cells.
Lin
S-J
SJ
Division of Asthma, Allergy and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University, Taoyuan, Taiwan. sjlino@adm.cgmh.org.tw
Cheng
P-J
PJ
Hsiao
S-S
SS
D018821:CD18 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D018821:CD18 Antigens; D016207:Cytokines; D019409:Interleukin-15