Characterization of an I-E-restricted, gp63-specific, CD4-T-cell clone from Leishmania major-resistant C3H mice that secretes type 2 cytokines and exacerbates infection with L. major.
A T-cell clone (designated KLmB-3) was derived from resistant C3H mice 2 weeks after infection with Leishmania major. KLmB-3 was a CD4-T-cell clone that utilized the V beta 8.1 T-cell receptor. When adoptively transferred to naive C3H mice, KLmB-3 unexpectedly exacerbated infection with L. major (it increased the cutaneous lesion size and the parasite burden within the lesion). The ability of KLmB-3 to exacerbate disease correlated with its ability to produce the type 2-associated cytokines interleukin-4 (IL-4), IL-5, IL-10, and transforming growth factor beta. Interestingly, KLmB-3 was specific for an epitope in the amino-terminal end of the L. major surface gp63 zinc metalloproteinase (leishmanolysin) that has been shown to be capable of inducing a protective immune response. Moreover, KLmB-3 was activated when this epitope was presented in the context of H-2 I-E rather than H-2 I-A.
Theodos
Cynthia M
CM
Biogen, Inc., Cambridge, Massachusetts 02142, USA.
Morris
Robin V
RV
Bishop
Jeanette V
JV
Jones
Jeremy D
JD
McMaster
W Robert
WR
Titus
Richard G
RG
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D018320:Leishmania major / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology*; D008213:Lymphocyte Activation; D008666:Metalloendopeptidases / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania