IL-4 enhances long-term survival of CD28-deficient T cells.
CD28 signaling is critical for IL-2 production by established Th1 clones, but CD28 does not appear to play a role in the activation of established Th2 clones. To determine the role of CD28 in the generation of polarized T cells, clones were derived using cells from CD28-deficient (CD28-/- mice, which had been bred with mice that express the DO11.10 transgene, a CD4+ TCR-alphabeta receptor that recognizes OVA peptide 323-339 bound to I-Ad. Most T cell clones derived from CD28+/+ mice survived multiple stimulations, while T cell clones derived from CD28-/- mice survived only if they were derived initially in the presence of IL-4 or both IL-2 and IL-4. Signaling through the CD28 molecule did not appear to be important in the initial activation of T cell clones, as the precursor frequency of clones derived from normal (CD28+/+) and CD28-/- mice was similar. Primary stimulation in the presence of IL-4 increased cell number and viability of both CD28+/+ and CD28-/- T cells in primary culture. However, the survival of CD28-/- cells is more dependent on IL-4 than is the survival of CD28+/+ cells. The continued presence of anti-IL-4 mAb dramatically decreased the number of viable cells in the CD28-/- cultures but had little effect on the viability of the CD28+/+ clones. Thus, initial culture with IL-4 allows the isolation of CD28-/- T cell clones that produce IL-4. In these clones, IL-4 acts as both an autocrine growth and survival factor.
Stack
R M
RM
Department of Pathology, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, IL 60637, USA.
Thompson
C B
CB
Fitch
F W
FW
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D018106:CD28 Antigens / Q000235:genetics* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D018106:CD28 Antigens; D007376:Interleukin-2; D015847:Interleukin-4