Anti-CD3 antibodies induce T cells from unprimed animals to secrete IL-4 both in vitro and in vivo.
Recently, functional heterogeneity among Th cells has been recognized. Based on pattern of lymphokine secretion, two mutually exclusive subsets of CD4+ cells have been defined and designated Th1 (secreting IL-2 and IFN-gamma) and Th2 (secreting IL-4 and IL-5). Identification of these subsets was mostly based on the study of long term cultured T cell lines and clones, and little is known about the Th heterogeneity in vivo. In particular, it has been suggested that IL-4 producing cells cannot be detected in vivo or in primary stimulations in vitro unless responder cells had been previously primed. Our data however, indicate that anti-CD3 mediated stimulation can induce T cells isolated from unprimed animals to IL-4 production. An assay system based on the ability of IL-4 to increase Ia expression of B cells present in the environment of activated T cells was found to be more sensitive than detection of secreted IL-4 in the supernatant by conventional bioassays and was used to study IL-4 production by unprimed lymphocytes polyclonally stimulated in vivo and in vitro by anti-CD3 mAb. The results obtained indicate that CD4+ CD8- T cells able to produce IL-4 upon receptor-specific stimulation exist in the preimmune pool of adult animals. Remarkably, these cells can also be stimulated in vivo by treating animals with anti-CD3 mAb, as indicated by the in vivo induction of IL-4 specific mRNA and hyper-Ia expression on B cells. These results indicate that the inability to detect IL-4 in primary cultures is not due to different activation requirements of Th2 cells but may simply result from their lower frequency in unprimed animals.
Flamand
V
V
Département de Biologie Moléculaire, Université Libre de Bruxelles, Belgium.
Abramowicz
D
D
Goldman
M
M
Biernaux
C
C
Huez
G
G
Urbain
J
J
Moser
M
M
Leo
O
O
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude / Q000276:immunology; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003524:Cyclosporins; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4