Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin 12 and Pentostam.
Successful treatment in allergic, autoimmune, and infectious diseases often requires altering the nature of a detrimental immune response mediated by a particular CD4+ T helper (Th) cell subset. While several factors contribute to the development of CD4+ Th1 and Th2 cells, the requirements for switching an established response are not understood. Here we use infection with Leishmania major as a model to investigate those requirements. We report that treatment with interleukin 12 (IL-12), in combination with the antimony-based leishmanicidal drug Pentostam, induces healing in L. major-infected mice and that healing is associated with a switch from a Th2 to a Th1 response. The data suggest that decreasing antigen levels may be required for IL-12 to inhibit a Th2 response and enhance a Th1 response. These observations are important for treatment of nonhealing forms of human leishmaniasis and also demonstrate that in a chronic infectious disease an inappropriate Th2 response can be switched to an effective Th1 response.
Nabors
G S
GS
Department of Pathobiology, University of Pennsylvania, Philadelphia 19104, USA.
Afonso
L C
LC
Farrell
J P
JP
Scott
P
P
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D018664:Interleukin-12 / Q000627:therapeutic use*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000628:therapy*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D012333:RNA, Messenger; D018664:Interleukin-12; D000967:Antimony Sodium Gluconate