IL-6 increases primed cell expansion and survival.
Cytochrome c-specific CD4 T cells from transgenic donors transferred to syngeneic B10.A mice expand more vigorously upon immunization if exogenous IL-6 is provided during the initial phase of immunization. The resultant increase in the frequency and number of Ag-specific cells is observed in the blood, lymph nodes, spleen, liver, and lung and persists for at least 3 mo. Treatment of immunized recipients with anti-IL-6 or use of IL-6 knockout recipients reduced the frequency of Ag-specific CD4 T cells during a comparable period, indicating that IL-6 is physiologically involved in the expansion of memory and/or effector cells and thus in the persistence of memory. IL-6 did not alter the duration of Ag-presenting activity. Both CFSE dilution studies and labeling with BrdU indicated that IL-6 does not effect proliferative rates of responding CD4 T cells. By contrast, annexin V staining was diminished in responding cells from the IL-6-treated animals, particularly among those cells that had undergone five or more divisions. These results indicate that IL-6 reduces the level of apoptosis among Ag-stimulated cells; thus, it plays a central role in determining numbers of memory and/or effector CD4 T cells in response to immunization over extended periods.
Rochman
Irina
I
Lautenberg Center for General and Tumor Immunology, Hadassah-Hebrew University Medical School, Jerusalem, Israel.
Paul
William E
WE
Ben-Sasson
S Z
SZ
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007156:Immunologic Memory; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D017710:Lymphocyte Transfusion; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014185:Transplantation, Isogeneic; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors