The Development of a Th1-Type Response and Resistance toLeishmania majorInfection in the Absence of CD40-CD40L Costimulation

作者: Udaikumar M. Padigel , Peter J. Perrin , Jay P. Farrell

DOI: 10.4049/JIMMUNOL.167.10.5874

关键词: LymphReceptorCD28Leishmania majorImmunologyCD40Molecular biologyLesionImmune systemBiologyMessenger RNA

摘要: CD40-CD40L interactions have been shown to be essential for the production of IL-12 and IFN-γ control L. major infection. In contrast, C57BL/6 mice deficient in CD28 develop a dominant Th1-type response heal this study, we investigate effects deficiency both CD40L molecules on immune course We compared infection genetically lacking (CD40L−/−), (CD28−/−), or (CD40L−/−CD28−/−), mice, all resistant background. Although CD40L−/− failed infection, CD28−/− CD40L−/−CD28−/− as well spontaneously resolved their infections. Healing had reduced numbers lesion parasites with nonhealing mice. At wk 9 detected similar levels IL-4, IFN-γ, IL-12p40, IL-12Rβ2 mRNA draining lymph nodes healing C57BL/6, CD28−/−, whereas increased IL-4 but IL-12Rβ2. separate experiment, blocking pathway using Ab led an exacerbation little no effect Together, these results demonstrate that absence costimulation, interaction is not required development protective response. The expression IL-12Rβ2, further suggests presence additional stimulus capable regulating its receptors interactions.

参考文章(46)
Bo Wang, Robert Maile, Roberta Greenwood, Edward J. Collins, Jeffrey A. Frelinger, Naive CD8+ T Cells Do Not Require Costimulation for Proliferation and Differentiation into Cytotoxic Effector Cells The Journal of Immunology. ,vol. 164, pp. 1216- 1222 ,(2000) , 10.4049/JIMMUNOL.164.3.1216
P Natovitz, P Scott, E Pearce, A Sher, Vaccination against cutaneous leishmaniasis in a murine model. I. Induction of protective immunity with a soluble extract of promastigotes. Journal of Immunology. ,vol. 139, pp. 221- 227 ,(1987)
Peter S. Linsley, Richard M. Locksley, David B. Corry, Steven L. Reiner, DIFFERENTIAL EFFECTS OF BLOCKADE OF CD28-B7 ON THE DEVELOPMENT OF TH1 OR TH2 EFFECTOR CELLS IN EXPERIMENTAL LEISHMANIASIS Journal of Immunology. ,vol. 153, pp. 4142- 4148 ,(1994)
Hayo Himmelrich, Pascal Launois, Ivan Maillard, Tilo Biedermann, Fabienne Tacchini-Cottier, Richard M. Locksley, Martin Röcken, Jacques A. Louis, In BALB/c Mice, IL-4 Production During the Initial Phase of Infection with Leishmania major Is Necessary and Sufficient to Instruct Th2 Cell Development Resulting in Progressive Disease Journal of Immunology. ,vol. 164, pp. 4819- 4825 ,(2000) , 10.4049/JIMMUNOL.164.9.4819
J C Cerottini, R Ceredig, J A Louis, R G Titus, Therapeutic effect of anti-L3T4 monoclonal antibody GK1.5 on cutaneous leishmaniasis in genetically-susceptible BALB/c mice. Journal of Immunology. ,vol. 135, pp. 2108- 2114 ,(1985)
P E Fields, F W Fitch, A I Sperling, J A Bluestone, I C Rulifson, CD28 costimulation promotes the production of Th2 cytokines. Journal of Immunology. ,vol. 158, pp. 658- 665 ,(1997)
Teresa Bement, Marcos A. Rossi, Thelma A. Koppi, William C. Fanslow, Pamela Ovendale, Mark R. Alderson, Antonio Campos-Neto, CD40 ligand is not essential for the development of cell-mediated immunity and resistance to Mycobacterium tuberculosis Journal of Immunology. ,vol. 160, pp. 2037- 2041 ,(1998)
Shinobu Imajoh-Ohmi, Hideo Nariuchi, Hidehiro Yamane, Osamu Igarashi, IL-12 Receptor (IL-12R) Expression and Accumulation of IL-12Rβ1 and IL-12Rβ2 mRNAs in CD4+ T Cells by Costimulation with B7-2 Molecules Journal of Immunology. ,vol. 160, pp. 1638- 1646 ,(1998)
R. M. Locksley, Farrah Hatam, F. P. Heinzel, R. M. Rerko, IL-2 is necessary for the progression of leishmaniasis in susceptible murine hosts. Journal of Immunology. ,vol. 150, pp. 3924- 3931 ,(1993)
Nancy Noben-Trauth, David L. Sacks, William E. Paul, IL-4- and IL-4 Receptor-Deficient BALB/c Mice Reveal Differences in Susceptibility to Leishmania major Parasite Substrains Journal of Immunology. ,vol. 162, pp. 6132- 6140 ,(1999)