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Infection and Immunity, March 2003, p. 1389-1395, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1389-1395.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

CD40-CD40 Ligand Costimulation Is Not Required for Initiation and Maintenance of a Th1-Type Response to Leishmania major Infection

Udaikumar M. Padigel and Jay P. Farrell*

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Received 27 September 2002/ Returned for modification 25 November 2002/ Accepted 4 December 2002

Although previous studies demonstrated a requirement for CD40-CD40 ligand (CD40L) interaction in the development of resistance to Leishmania infection, we recently showed that mice lacking the gene for CD40L (CD40L-/- mice) can control Leishmania major infection when they are infected with reduced numbers of parasites. In this study, we examine the cytokine pattern in healing versus nonhealing CD40L-/- mice and investigated whether CD40 activation is required for resistance to reinfection. We observed that CD4+ cells in healed CD40L-/- mice produce high levels of gamma interferon compared to cells from nonhealing, high-dose-inoculated mice. In addition, we observed a higher frequency of interleukin-12 (IL-12)- producing cells and a reduced number of IL-4-producing cells in mice infected with reduced numbers of parasites. Importantly, we found that healed CD40L-/- mice are highly resistant to reinfection with a large parasite inoculum. In addition, by comparing the cytokine patterns at an early and late stage of infection in nonhealing CD40L-/- mice, we demonstrated that nonhealing CD40L-/- mice produce a weak Th1-type response during the early stage of infection, but this response wanes as a Th2-type response emerges during late stages of infection. Anti-IL-4 antibody treatment, starting either at the beginning of infection or at week 4 postinfection enabled CD40L-/- mice to control a high-dose infection. Together, these results show that CD40-CD40L interaction, although important for IL-12 production in high-dose infections, is not required for either the development or maintenance of resistance in mice infected with reduced numbers of parasites.

* Corresponding author. Mailing address: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA 19104. Phone: (215) 898-8561. Fax: (215) 573-7023. E-mail: farrellj{at}vet.upenn.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, March 2003, p. 1389-1395, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1389-1395.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Xu, G., Liu, D., Okwor, I., Wang, Y., Korner, H., Kung, S. K. P., Fu, Y.-X., Uzonna, J. E. (2007). LIGHT Is Critical for IL-12 Production by Dendritic Cells, Optimal CD4+ Th1 Cell Response, and Resistance to Leishmania major. J. Immunol. 179: 6901-6909 [Abstract] [Full Text]  
  • Hewitson, J. P., Hamblin, P. A., Mountford, A. P. (2007). In the Absence of CD154, Administration of Interleukin-12 Restores Th1 Responses but Not Protective Immunity to Schistosoma mansoni. Infect. Immun. 75: 3539-3547 [Abstract] [Full Text]  
  • Padigel, U. M., Kim, N., Choi, Y., Farrell, J. P. (2003). TRANCE-RANK Costimulation is Required for IL-12 Production and the Initiation of a Th1-Type Response to Leishmania major Infection in CD40L-Deficient Mice. J. Immunol. 171: 5437-5441 [Abstract] [Full Text]  


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