Regulatory T-cell subset analysis and profile of interleukin  (IL)-10, IL-17 and interferon-gamma cytokine-producing cells  in kidney allograft recipients with donor cells infusion.
BACKGROUND
This pilot study aimed to assess whether the perioperative infusion of donor bone marrow cells (DBMC) in renal allograft recipients can affect the appearance of peripheral regulatory T-cell subsets and the profile of cytokine-producing cells [interferon-gamma (IFN-γ), interleukin (IL)-17 and IL-10] 2 years after transplantation.


METHODS
Fresh blood samples were collected from 14 kidney recipients who received infusion and from 13 kidney recipients without infusion who served as controls at the end of the second post-transplantation year. Initially the percentages of CD4(+)CD25(+)FoxP3(+) T cells and CD3(+)CD8(+)CD28(-) T cells were quantified using flowcytometry. Thereafter, the frequencies of IL-10-, IL-17- and IFN-γ-producing cells were determined separately using the ELISPOT technique with peptides corresponding to mismatched donor HLA-DR molecules and phytohemagglutinin (PHA).


RESULTS
The mean numbers of IFN-γ- and IL-17-producing cells in response to PHA were lower in infused patients than in controls (P = 0.02 and P = 0.18, respectively); however, an increased frequency of IL-10-producing cells was observed compared to controls (P = 0.07). Furthermore, the ratio of IL-10/IFN-γ-producing cells was significantly higher in the DBMC-infused group versus controls (P = 0.01). There was a negative correlation between the percentage of CD3(+)CD8(+)CD28(-)T cells and IL-17-producing cells in the infused group (r = -0.539, P = 0.04). The mean levels and the frequency of microchimerism within the first post-transplantation year were also significantly higher in infused patients than in controls (P = 0.007 and P = 0.001, respectively).


CONCLUSIONS
Our findings suggest that DBMC infusion could partially stimulate the regulatory mechanisms against alloimmune responses in kidney allograft recipients
Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences, Poursina Ave, Tehran, Iran.
Moslem
M
Ranjbar
Ghasem
G
Solgi
Mousa
M
Mohammadnia
Behrouz
B
Nikbin
Gholamreza
G
Pourmand
Bita
B
Ansaripour
Aliakbar
A
Amirzargar
D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D014184:Transplantation, Homologous
D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D007371:Interferon-gamma