Table 7.

Xenogeneic rejection mechanism in orthotopic corneal xenotransplantation using small to medium animal models with variant donors except pig.

Recipient type	References	Type (PKP/lamella)	Donor		Recipient	Donor size (mm)	N	AST or MST	Histology of the rejected grafts/serum/DLN
Rat	(Ross et al., 1993, 1994)	PKP	Guinea pig		Lewis ACI	3.5	10	8 D	•OX-19+ T cells, OX-42+ neutrophils/macrophages •Ig M & Ig G ↑↑ (graft/serum)
					Lewis ACI (+xeno-skin graft)		8	5 D	•Ig G ↑↑↑ (graft)
	Larkin and Williams (1995)	PKP	Guinea pig		Fischer 344	3.0	NA	3 D	•CD4+ & CD8+ T cells, macrophages, eosinophils, neutrophils •Anti-rat Ig G2a/Ig M •Preformed natural Ab (serum)
					CBH-rnu/rnu (athymic)		NA	3 D	•Few cells in graft (No eosinophil) •Preformed natural Ab (serum)
			Chicken		Fischer 344		NA	2 D	•CD4+ & CD8+ T cells, macrophages, eosinophils, neutrophils •Anti-rat Ig G/Ig M •Preformed natural Ab (serum)
Mouse	Tanaka et al. (2000)	PKP	Guinea pig		C.B-17SCID	2.0	8	>56 D††
					C57BL/6		15	10 D	•Many infiltrating cells •Anti– guinea pig Ig G ↑ (serum)
					BALB/c		10	16 D	•Anti– guinea pig Ig G ↑ (serum)
					μ KO		15	8 D
					C3 KO		13	21 D††
					β-2 KO		14	9 D
					CD4 KO		11	27 D††
	Tanaka et al. (2001)	PKP	Guinea pig		Class II KO	2.0	11	31 D††
	Yamagami et al. (1997)	PKP	Rat (Lewis)		BALB/c (H2d)	2.0	13	5.8 D	•CD3+ T cells, B cells, neutrophils, mouse Ig G, Ig M & C3 •Xenoreactive Ig G & Ig M (serum)
					BALB/c (H2d) (+FK506/anti-LFA-1 mAb)		9	67.7 D†††	•Ig G ↓ •Ig M & C3, CD3+ T & B cell not detected on D6 -D10 •Xenoreactive Ig G & Ig M ↓ (serum)
	Pindjakova et al. (2005)	PKP	Rat (Lewis)		BALB/c	2.0	11	8 D
					BALB/c (+anti CD4 Ab)		7	16.9 D†††
					BALB/c (+anti CD8 Ab)		11	8.9 D
	Sedlakova et al. (2005)	PKP	Sprague-Dawley rats		BALB/c (+FTY720, 3 mg/kg/d)	2.0	5	15.6 D†††	•CD3+ T & B cells, macrophages, CD11c cell ↓ c/w control •CD3+ T & B cells, macrophages, CD11c cell ↓ c/w control in DLN
	Holan et al. (2005)	PKP	Rat (Lewis)		BALB/c (+donor-specific anti-sera)	2.0	8	7.4 D*
					BALB/c (+anti CD4 Ab)		10	44.1 D
					BALB/c (+donor-specific anti-sera/anti CD4 Ab)		8	21.5 D**
		PKP		Guinea pig	CB.17 SCID (+Whole splenocytes)	2.0	13	15 D
					CB.17 SCID (+CD4+ T cell-depleted splenocytes)			27 D***		•CD8+ IFNγ+ T cells •No cytotoxic CD8+ T cells
					CB.17 SCID (+CD4+/CD8+ T cell-depleted splenocytes)			49 D
Medium	Babel and Bourquin (1952)	lamellar		ox, sheep, horse, pig, guinea-pig, rabbit, human	rabbit	5	30	1 W-3.5 M		•Eosinophils
	Faber et al. (2009)	PKP		human	pig	NA	1	15 D		•Lymphocytes, histiocytes, eosinophils, neutrophils •Preformed Ig M (serum) •Th1 (IFN-γ) & Th2 (IL-4) ↑ in PBMC

Abbreviations: Ab: antibody, AST: average survival time, c/w: compared with, D: days, DLN: drainage lymph node, KO: knockout, LFA: leukocyte function-associated antigen, M: months, mAb: monoclonal antibody, MST: median survival time, N: number of animals experimented, NA: not available, PBMC: peripheral blood mononuclear cell, W: weeks.

Significantly increased survival compared with that of wild-type control^††, or with that of control^†††

Significantly shortened survival compared with that of control (9.4 D)* or with that of anti CD4 Ab treated group (44.1 D)**.

Significantly shortened survival compared with that of SCID reconstituted with CD4⁺/CD8⁺ T cell-depleted splenocytes (49 D) *** and increased survival compared with that of SCID reconstituted with whole splenocytes (15 D)***.