Asymmetry in the atmosphere of the ultra-hot Jupiter WASP-76 b
Immunotherapy
1. CD4+CD25+ T Regulatory Suppress NK Cell-
Mediated Immunotherapy of Cancer
(Mark j.smyth, Michel W.L.Teng, Dale.I.Godfrey)
SUBHAM PREETAM
Master In Biotechnology
2. ABSTRACT
• CD4+ CD25+ Regulatory T cell that suppress T cell
mediated immune responses may also regulate other
arms of an effective immune response.
• Treg directly inhibit NKG2D-mediated NK cell
cytotoxicity in vitro and in vivo, effectively
suppressing NK cell mediated tumour rejection.
• Treg were shown to inhibit NKG2D-mediated
cytolysis largely by a TGF-β-Dependent mechanism
and independently IL-10.
3. INTRODUCTION
• CD4+CD25+ T regulatory are unique population of T cells that
maintain immune tolerance and are critical in host suppression of
organ specific auto immune diseases.
• Treg also contribute to elicit a dominant tolerance during infection and
allogenic transplantation and suppress immune responses to tumours.
• Depletion of Treg in mice with anti IL-2 receptor or low dose
cyclophosphamide depletion of Treg improves in T cell based tumour
clearance.
• NK cells are regulated by cytokines in the environment and when
interacting with tumour directly there is a delicate balance between
inhibitory signals mediated by MHC class I molecules and activating
signals triggered by specific ligands.
4. MATERIALS AND METHODS
Mice
I. Inbread C57 BL/6 and BLLB/c Wild type mice are purchased from
the Walter and Elisa all institute of Medical reserch the B6 RAG gene
targeted mice were Ten generation back crossed to B6 and were breed
at the Peter MacCallum cancer center.
Isolation of spleen NK cell Treg and cytotoxicity assay.
Flow cytometric analysis.
Tumour cell lines.
Tumour model in vivo.
NK and CD8 cell depletion.
Statistical analysis
6. DISCUSSION
• Although earlier studies have suggested a role for Treg in suppressing NK cell
effector functions in vitro (6,32,33),we have defined at least one mechanism by
which activated Treg can directly suppress NK cell function via the NKG2D
pathways in vivo.
• We do not want to suggest that the effect og Treg on NK cell function may be
simplistic; indeed, to the contrary, Treg may suppress NK cell function by a
number of different mechanisms.
• Interestingly, we were unable to detect any down-regulation of NKG2D on NK
cells when exposed to activated Treg (data not shown).
• However, in vivo, even relatively few transferred activated Treg (compared with
host NK cells)suppressed NK cell-mediated control of tumour metastases.
• NK cell function in cancer patients is often severely impaired, and it will be of
interest to determine whether an inverse relationship between NK cell activation
and cytotoxicity and Treg expansion is detected in these patients.