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Allogeneic lymphocyte transfer in MHC-identical siblings and MHC-identical unrelated Mauritian cynomolgus macaques.

Mee ET, Stebbings R, Hall J, Giles E, Almond N, Rose NJ - PLoS ONE (2014)

Bottom Line: Recent advances in our understanding of the Major Histocompatibility Complex diversity of Mauritian cynomolgus macaques enabled the establishment of a breeding program to generate Major Histocompatibility Complex (MHC)-identical animals.Results indicated that peripheral persistence kinetics were comparable following infusion by different routes, and that cells were detectable at equivalent levels in lymphoid tissues six weeks post-infusion.Donor lymphocytes were detectable at higher levels in MHC-identical siblings compared with unrelated animals, however the total time of persistence did not differ.

View Article: PubMed Central - PubMed

Affiliation: Division of Virology, National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, South Mimms, Hertfordshire, United Kingdom.

ABSTRACT
The detailed study of immune effector mechanisms in primate models of infectious disease has been limited by the inability to adoptively transfer lymphocytes from vaccinated animals into naïve immunocompetent recipients. Recent advances in our understanding of the Major Histocompatibility Complex diversity of Mauritian cynomolgus macaques enabled the establishment of a breeding program to generate Major Histocompatibility Complex (MHC)-identical animals. The current study utilised this resource to achieve an improved model of adoptive transfer of lymphocytes in macaques. The effect of route of transfusion on persistence kinetics of adoptively transferred lymphocytes was evaluated in an autologous transfer system. Results indicated that peripheral persistence kinetics were comparable following infusion by different routes, and that cells were detectable at equivalent levels in lymphoid tissues six weeks post-infusion. In a pilot-scale experiment, the persistence of adoptively transferred lymphocytes was compared in MHC-identical siblings and MHC-identical unrelated recipients. Lymphocytes transferred intra-peritoneally were detectable in the periphery within one hour of transfer and circulated at detectable levels in the periphery and lymph nodes for 10 days. Donor lymphocytes were detectable at higher levels in MHC-identical siblings compared with unrelated animals, however the total time of persistence did not differ. These results demonstrate a further refinement of the lymphocyte adoptive transfer system in Mauritian cynomolgus macaques and provide a foundation for hitherto impractical experiments to investigate mechanisms of cellular immunity in primate models of infectious disease.

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Detection of adoptively transferred allogeneic lymphocytes in lymphoid tissues of recipient animals at days 22, 35 and 36 post-transfer.Dashed line indicates threshold for detection of CFDA-SE+ cells. Animals are colour-coded by experimental group: black MHC-identical siblings; red MHC-identical unrelated; blue MHC-mismatched.
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pone-0088670-g003: Detection of adoptively transferred allogeneic lymphocytes in lymphoid tissues of recipient animals at days 22, 35 and 36 post-transfer.Dashed line indicates threshold for detection of CFDA-SE+ cells. Animals are colour-coded by experimental group: black MHC-identical siblings; red MHC-identical unrelated; blue MHC-mismatched.

Mentions: One animal from each experimental group was sacrificed at day 22 and spleen, mesenteric lymph nodes (MLN) and peripheral lymph nodes (PLN) were sampled. CFDA-SE-labelled cells were undetectable in all samples (Fig. 3). The remaining four animals were sacrificed at day 35-36 post-transfer and samples taken as above. Low level CFDA-SE+ populations were observed in the MLN of two animals – however, the absolute number of events was low (10–13 of one million events) and the signal was close to the threshold of detection. Together these results indicate that persistence of cells in the tissues was either low level or undetectable regardless of experimental group.


Allogeneic lymphocyte transfer in MHC-identical siblings and MHC-identical unrelated Mauritian cynomolgus macaques.

Mee ET, Stebbings R, Hall J, Giles E, Almond N, Rose NJ - PLoS ONE (2014)

Detection of adoptively transferred allogeneic lymphocytes in lymphoid tissues of recipient animals at days 22, 35 and 36 post-transfer.Dashed line indicates threshold for detection of CFDA-SE+ cells. Animals are colour-coded by experimental group: black MHC-identical siblings; red MHC-identical unrelated; blue MHC-mismatched.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921199&req=5

pone-0088670-g003: Detection of adoptively transferred allogeneic lymphocytes in lymphoid tissues of recipient animals at days 22, 35 and 36 post-transfer.Dashed line indicates threshold for detection of CFDA-SE+ cells. Animals are colour-coded by experimental group: black MHC-identical siblings; red MHC-identical unrelated; blue MHC-mismatched.
Mentions: One animal from each experimental group was sacrificed at day 22 and spleen, mesenteric lymph nodes (MLN) and peripheral lymph nodes (PLN) were sampled. CFDA-SE-labelled cells were undetectable in all samples (Fig. 3). The remaining four animals were sacrificed at day 35-36 post-transfer and samples taken as above. Low level CFDA-SE+ populations were observed in the MLN of two animals – however, the absolute number of events was low (10–13 of one million events) and the signal was close to the threshold of detection. Together these results indicate that persistence of cells in the tissues was either low level or undetectable regardless of experimental group.

Bottom Line: Recent advances in our understanding of the Major Histocompatibility Complex diversity of Mauritian cynomolgus macaques enabled the establishment of a breeding program to generate Major Histocompatibility Complex (MHC)-identical animals.Results indicated that peripheral persistence kinetics were comparable following infusion by different routes, and that cells were detectable at equivalent levels in lymphoid tissues six weeks post-infusion.Donor lymphocytes were detectable at higher levels in MHC-identical siblings compared with unrelated animals, however the total time of persistence did not differ.

View Article: PubMed Central - PubMed

Affiliation: Division of Virology, National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, South Mimms, Hertfordshire, United Kingdom.

ABSTRACT
The detailed study of immune effector mechanisms in primate models of infectious disease has been limited by the inability to adoptively transfer lymphocytes from vaccinated animals into naïve immunocompetent recipients. Recent advances in our understanding of the Major Histocompatibility Complex diversity of Mauritian cynomolgus macaques enabled the establishment of a breeding program to generate Major Histocompatibility Complex (MHC)-identical animals. The current study utilised this resource to achieve an improved model of adoptive transfer of lymphocytes in macaques. The effect of route of transfusion on persistence kinetics of adoptively transferred lymphocytes was evaluated in an autologous transfer system. Results indicated that peripheral persistence kinetics were comparable following infusion by different routes, and that cells were detectable at equivalent levels in lymphoid tissues six weeks post-infusion. In a pilot-scale experiment, the persistence of adoptively transferred lymphocytes was compared in MHC-identical siblings and MHC-identical unrelated recipients. Lymphocytes transferred intra-peritoneally were detectable in the periphery within one hour of transfer and circulated at detectable levels in the periphery and lymph nodes for 10 days. Donor lymphocytes were detectable at higher levels in MHC-identical siblings compared with unrelated animals, however the total time of persistence did not differ. These results demonstrate a further refinement of the lymphocyte adoptive transfer system in Mauritian cynomolgus macaques and provide a foundation for hitherto impractical experiments to investigate mechanisms of cellular immunity in primate models of infectious disease.

Show MeSH
Related in: MedlinePlus