Costimulation of IL-4 production by murine B7-1 and B7-2 molecules.
We have examined the capacity of murine B7-1 and B7-2 to costimulate the production of IL-4 by murine CD4+ T lymphocytes. Cloned and freshly isolated T cells were incubated with the anti-CD3 mAb 145-2C11 in the presence of Chinese hamster ovary (CHO) cells that stably express murine B7-1 and B7-2 at comparable levels. IL-4 protein levels were measured in culture supernatants by the CT.4S bioassay, and levels of IL-4 mRNA were determined by semiquantitative reverse transcription-PCR. Both B7-1- and B7-2-transfected CHO cells, but not CHO control transfectants, were able to costimulate IL-4 production. Similarly, both B7-1 and B7-2 could up-regulate IFN-gamma mRNA levels. Cell fractionation experiments on freshly isolated CD4+ T lymphocytes revealed that the costimulatory potential of B7-1 and B7-2 for IL-4 production was restricted to CD44high T cells, i.e., the subpopulation that contains recently activated and memory cells. CD44low, naive CD4+ T lymphocytes, could only be induced to produce IL-4 by repeated stimulation with B7 transfectants. In summary, we have not detected qualitative differences in the capacities of murine B7-1 and B7-2 to induce IL-4 production. The results of our experiments, therefore, argue against the recent hypothesis that precursor Th cells are directed toward the Th2 phenotype by B7-2 and toward the Th1 phenotype by B7-1.
Natesan
M
M
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Razi-Wolf
Z
Z
Reiser
H
H
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000235:genetics / Q000494:pharmacology*; D051940:B7-2 Antigen; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*; D016466:CHO Cells; D002999:Clone Cells; D006224:Cricetinae; D004357:Drug Synergism; D018960:Hyaluronan Receptors / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000302:isolation & purification; D014162:Transfection / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma