In vivo blocking of L-selectin rescues BALB/c mice from fatal Leishmania major infection.
Susceptibility and resistance to experimental Leishmania major (L. major) infection in mice are associated with a Th2- or Th1-type response, respectively. We have previously shown that immunological events occurring within the first 24 h after infection in the lymph node (LN) draining the site of parasite challenge are critical for the development of either type of T-cell responses. In the present study we manipulated these events by preventing the entry of naive lymphocytes into the draining LN by injecting BALB/c mice with a single dose of the anti-L-selectin mAb MEL-14 one day prior to infection with L. major. In contrast to control BALB/c mice, in MEL-14 treated animals the primary lesion healed 12 weeks after infection. The parasite load in the spleen and lymph nodes of MEL-14 treated mice was significantly reduced. The healing was found to be associated with an increased production of IFN-gamma and with a decrease in IL-4 production by LN cells. We observed a dramatic decrease in cellularity in the draining LN in Mel-14 treated L. major-infected mice within the first week of infection. Moreover, the cells in the LN of MEL-14 treated mice were highly enriched in activated cells as well as in cell influx in the draining LN after local L. major infection of BALB/c mice prevents fatal disease. The data suggest the MEL-14-induced enrichment of the draining LN in memory and activated cells is fundamental for the initiation of a protective Th1-type response.
Laskay
T
T
Institute for Clinical Microbiology and Immunology, University of Erlangen-Nuremberg, Germany. laskay@mikrobio.med.uni-erlangen.de
Wittmann
I
I
Diefenbach
A
A
Röllinghoff
M
M
Solbach
W
W
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D018960:Hyaluronan Receptors / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D019041:L-Selectin / Q000276:immunology*; D037181:Lectins, C-Type; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018960:Hyaluronan Receptors; D007371:Interferon-gamma; D007376:Interleukin-2; D015847:Interleukin-4; D019041:L-Selectin; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens