CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major.
Standard murine models of cutaneous leishmaniasis, involving s.c. inoculation of large numbers of Leishmania major promastigotes, have not supported an essential role for CD8(+) T cells in the control of primary infection. Recently, a L. major model combining two main features of natural transmission, low parasite dose and inoculation into a dermal site, has been established in resistant C57BL/6 mice. In the present studies, C57BL/6 mice with CD8(+) T cell deficiencies, including CD8(-/-) and CD8-depleted mice, failed to control the growth of L. major following inoculation of 100 metacyclic promastigotes into the ear dermis. The resulting dermal pathology was minor and delayed. Lesion formation in wild-type mice was coincident with the killing of parasites in the inoculation site. Both events were associated with the accumulation of CD8(+) T lymphocytes in the skin and with the capacity of CD8(+) T cells recovered from draining lymph nodes or infected dermis to release IFN-gamma following coculture with infected dendritic cells. Reconstitution of resistance to L. major in RAG(-/-) mice using T cells from naive donors was optimal when both CD4(+) and CD8(+) T cells were transferred. Primed CD8(+) T lymphocytes obtained from C57BL/6 mice during the acute stage of infection were able to mediate both pathology and immunity when transferred alone. The low dose, intradermal challenge model reveals that CD8(+) T cells play an essential role in both pathogenesis of and immunity to primary infection with L. major in the skin.
Belkaid
Yasmine
Y
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and Dermatology Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Von Stebut
Esther
E
Mendez
Susana
S
Lira
Rosalia
R
Caler
Elisabet
E
Bertholet
Sylvie
S
Udey
Mark C
MC
Sacks
David
D
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004254:DNA Nucleotidyltransferases / Q000172:deficiency / Q000235:genetics; D020405:Dermis / Q000276:immunology / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D004431:Ear, External; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis; D018320:Leishmania major / Q000254:growth & development / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics / Q000276:immunology*; D018345:Mice, Knockout; D045567:VDJ Recombinases
D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases