Priming by microbial antigens from the intestinal flora determines the ability of CD4+ T cells to rapidly secrete IL-4 in BALB/c mice infected with Leishmania major.
Infection of BALB/c mice with Leishmania major results in the rapid accumulation of IL-4 transcripts within CD4(+) T cells that react to the parasite Leishmania homologue of mammalian RACK1 (LACK) Ag. Because memory/effector cells secrete IL-4 more rapidly than naive cells, we sought to analyze the phenotype of these lymphocytes before infection. Indeed, a fraction of LACK-specific CD4(+) T cells expressed a typical CD62 ligand(low)CD44(high)CD45RB(low) phenotype in uninfected mice. LACK-specific T cells were primed in gut-associated lymphoid tissues by cross-reactive microbial Ags as demonstrated by their reactivity with bacterial extracts and by the ability of APCs from the mesenteric LN of BALB/c mice to induce their proliferation. Also, mice in which the digestive tract has been decontaminated exhibited a reduced proportion of LACK-specific T cells expressing a memory/effector phenotype and did not exhibit the early accumulation of IL-4 transcripts induced by L. major. Thus, LACK-specific T cells represent a subset of CD4(+) T cells which have acquired the ability to rapidly secrete IL-4 as the result of their priming by cross-reactive microbial Ags. Tracking the fate of these cells may provide information about the regulation of cell-mediated immune responses to gut Ags in physiological and pathological situations.
Julia
V
V
Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
McSorley
S S
SS
Malherbe
L
L
Breittmayer
J P
JP
Girard-Pipau
F
F
Beck
A
A
Glaichenhaus
N
N
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D004198:Disease Susceptibility; D013293:Enterococcus faecalis / Q000254:growth & development / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology; D005260:Female; D005856:Germ-Free Life / Q000276:immunology; D006825:Hybridomas; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D012333:RNA, Messenger; C114998:lacK protein, Agrobacterium tumefaciens; D015847:Interleukin-4