. Author manuscript; available in PMC: 2011 Jun 1.

Published in final edited form as: Expert Rev Hematol. 2010 Aug 1;3(4):469–483. doi: 10.1586/ehm.10.33

Table 1.

Changes in T-lymphocyte subpopulations in the spleens of mice under treatment with various immunomodulation protocols.

Immunomodulation protocols^†	Prevention of Factor VIII inhibitor formation	Modulation of pre-existing Factor VIII inhibitors	CD4⁺ T cells	Treg cells^‡ in CD4⁺ T cells	Activated^§ Factor VIII-specific Treg cells	Treg cells (total numbers)	Ref.
ITI (human protocol)^¶ ± immunosuppressant or intravenous immunoglobulin	Yes	Yes	No report	Possible increase	Possible increase	Possible increase	[22-25]
Mucosal or oral exposure of Factor VIII domain or peptides	Partial						[27]
Immature dendritic cells	Partial		No change	Increase	Increase	Increase	[29,30]
Apoptotic fibroblast cells	Partial	Partial			Increase		[31]
Neonatal gene transfer	Yes	NA	No change	Increase		Increase	[15,41,42]
Ex vivo HSC gene therapy + ATS	Yes	Yes					[43-46]
Gene therapy targeting liver, platelet or endothelial cells ± immunosuppressant	Yes or partial	Yes or partial					[48-50]
Cyclophosphamide	Partial		Decrease				[18,40,50]
Cyclosporin	Transient		Decrease				[55]
Rapamycin	Transient		Decrease				[55]
MMF	Transient		Decrease				[55]
CTLA4-Ig	Transient	Transient					[56,57]
IDO	Partial		Decrease				[58]
Anti-CD40-L	Transient	Transient					[22,56,57, 60,61]
CTLA4-Ig + CD40-L	Yes						[55]
Anti-inducible costimulatory molecule	Yes		Decrease	Increase	Increase	Slight increase	[66]
Anti-CD3	Yes	Partial	Decrease	Increase	Increase	No change	[72,73]
Adoptive Treg cell therapy	Partial	Transient	No change	Slight increase	Increase	Slight increase	[89]
IL-2–IL-2 monoclonal antibody complex	Yes		No change	Increase	Increase	Increase	[93]
Tolerogenic B-cell therapy	Yes	Partial	No change	Increase	Increase	Increase	[28,95,98]
Antimurine CD20 IgG₁ or IgG_2a	Partial	Transient and partial	No change	No change	No change	No change	[109,110]

^†

All immunomodulation therapies were applied in the presence of either Factor VIII protein or gene expression.

^‡

Treg cells denotes CD4⁺CD25⁺Foxp3⁺ Treg cells.

^§

Activated Treg cells are evaluated by expression of activation markers.

^¶

This is the human protocol for comparison purposes.

ATS: Anti-(murine)thymocyte serum; HSC: Hematopoietic stem cell; IDO: Indoleamine 2,3-dioxygenase; Ig: Immunoglobulin; ITI: Immune tolerance induction; MMF: Mycophenolate mophetil; NA: Not applicable.