Revealing the in vivo behavior of CD4+ T cells specific for an antigen expressed in Escherichia coli.
The clonal expansion and anatomic location of microbe-specific CD4+ Th cells was studied by tracking the fate of adoptively transferred DO11.10 TCR transgenic T cells specific for OVA peptide 323-339/I-Ad in BALB/c mice infected s.c. with Escherichia coli expressing a MalE-OVA fusion protein. After infection, the DO11.10 T cells accumulated in the T cell-rich paracortical regions of the draining lymph nodes, proliferated there for several days, and then moved into the B cell-rich follicles before they slowly disappeared from the lymph nodes. These changes occurred despite the fact that viable organisms were never found in the lymph nodes. The DO11.10 T cells also accumulated in the s.c. infection site, but about 1 day later than in the draining lymph nodes. Injection of purified MalE-OVA fusion protein alone induced a transient accumulation of DO11.10 T cells in the paracortical regions, but these T cells never entered follicles and the mice did not produce anti-OVA antibodies. The DO11.10 T cells that survived in animals injected with MalE-OVA alone were hyporesponsive to in vitro Ag restimulation and did not produce IL-2 and IFN-gamma, whereas DO11.10 T cells from mice infected with MalE-OVA-expressing bacteria produced both lymphokines. These results suggest that Ag-specific T cells are first activated in secondary lymphoid organs following primary bacterial infection and then migrate to the infection site. Furthermore, productive activation of the T cells during the primary response is dependent on bacterial components other than the Ag itself.
Chen
Z M
ZM
Department of Microbiology and Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Jenkins
M K
MK
D018528:ATP-Binding Cassette Transporters; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000096:biosynthesis* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D004927:Escherichia coli Infections / Q000276:immunology; D029968:Escherichia coli Proteins; D007108:Immune Tolerance; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D058619:Maltose-Binding Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D033902:Periplasmic Binding Proteins; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*; D012884:Skin Window Technique
D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D000939:Epitopes; D029968:Escherichia coli Proteins; C461619:MalE protein, E coli; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D010446:Peptide Fragments; D033902:Periplasmic Binding Proteins; D011993:Recombinant Fusion Proteins; C461599:maltose transport system, E coli; D010047:Ovalbumin