Inhibition of IL-2 induced IL-10 production as a principle of phase-specific immunotherapy.
Leishmania donovani, a protozoan parasite, inflicts a fatal disease, visceral leishmaniasis. The suppression of antileishmanial T cell responses that characterizes the disease was proposed to be due to deficiency of a T cell growth factor, IL-2. We demonstrate that during the first week after L. donovani infection, IL-2 induces IL-10 that suppresses the host-protective functions of T cells 14 days after infection. The observed suppression is concurrent with increased CD4+ glucocorticoid-induced TNF receptor+ T cells and Foxp3 expression in BALB/c mice, implicating IL-2-dependent regulatory T cell control of antileishmanial immune responses. Indeed, IL-2 and IL-10 neutralization at different time points after the infection demonstrates their distinct roles at the priming and effector phases, respectively, and establishes kinetic modulation of ongoing immune responses as a principle of a rational, phase-specific immunotherapy.
Bodas
Manish
M
National Centre for Cell Science, Ganeshkhind, Maharashtra, Pune 411-007, India.
Jain
Nitya
N
Awasthi
Amit
A
Martin
Sunil
S
Penke Loka
Raghu Kumar
RK
Dandekar
Dineshkumar
D
Mitra
Debashis
D
Saha
Bhaskar
B
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007167:Immunotherapy; D016753:Interleukin-10 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism*; D007893:Leishmania donovani / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10