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

• Published in: The Journal of immunology (1950) 2000-11, Vol.165 (10), p.5637-5645
• Main Authors: Julia, Valerie, McSorley, Stephen S, Malherbe, Laurent, Breittmayer, Jean-Philippe, Girard-Pipau, Fernand, Beck, Alain, Glaichenhaus, Nicolas
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Anti-Bacterial Agents - pharmacology; Antibodies, Monoclonal - administration & dosage; Antigens, Bacterial - immunology; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - immunology; Bacterial Proteins - genetics; Bacterial Proteins - immunology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Differentiation - immunology; Disease Susceptibility; Enterococcus faecalis - growth & development; Enterococcus faecalis - immunology; Epitopes, T-Lymphocyte - immunology; Escherichia coli - growth & development; Escherichia coli - immunology; Female; Germ-Free Life - immunology; Hybridomas; Injections, Intraperitoneal; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Interleukin-4 - immunology; Interleukin-4 - metabolism; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Leishmania major - immunology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - microbiology; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, Transgenic; Molecular Sequence Data; RNA, Messenger - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.10.5637

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.