Decreased IL-10 and IL-13 production and increased CD44(hi) T cell recruitment contribute to Leishmania major immunity induced by non-persistent parasites

Kedzierski, L; Curtis, JM; Doherty, PC; Handman, E; Kedzierska, K

Author(s): Kedzierski, L; Curtis, JM; Doherty, PC; Handman, E; Kedzierska, K;
Details: Publication Year 2008-11,Volume 38,Issue #11,Page 3090-3100
Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Leishmaniasis is currently classified as category 1 disease, i.e. emerging and uncontrolled. Since the importance of persistent infection for maintaining an effective long-lasting protective response is controversial, the present study asks whether immunisation with non-persistent parasites leads to protection against Leishmania infection and to the recruitment of T cells of a specific phenotype. Our study shows that vaccination of susceptible BALB/c mice with live Leishmania major phosphomannomutase-deficient parasites, which are avirulent and non-persistent in vivo, leads to protection against infection. Immunisation with phosphomannomutase-deficient parasites neither leads to differences in IFN-gamma, IL-12, IL-4 production nor alters the expression of effector and memory markers, including CD62L, IL-7R alpha and IL-2R alpha, when compared with unvaccinated controls. Observed protection is due to the ability of vaccinated. animals to suppress early IL-10 and IL-13 production and to recruit a higher number of antigen-experienced CD44(hi) CD4(+) and CD44(hi)CD8(+) T cells into draining LN following infection. Thus, expansion of T-cell numbers and their rapid recruitment to LN upon infection as well as the restriction of IL-13 and IL-10 production leading to high IFN-gamma/IL-10 ratio play an important role in protection against Leishmania affecting the outcome of the disease in favour of the host.
Publisher: WILEY-BLACKWELL
Keywords: CUTANEOUS LEISHMANIASIS; MEXICANA PHOSPHOMANNOMUTASE; TH1 RESPONSE; IFN-GAMMA; MEMORY; MICE; INFECTION; CD8(+); VACCINATION; SUSCEPTIBILITY
Publisher's Version: https://doi.org/10.1002/eji.200838423
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-11-01 12:00:00