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Pollen-induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis.

Desai MB, Gavrilova T, Liu J, Patel SA, Kartan S, Greco SJ, Capitle E, Rameshwar P - Clin Transl Immunology (2013)

Bottom Line: In cases with reduced inflammation, MSCs could become immune-enhancer cells.The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests.This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

View Article: PubMed Central - PubMed

Affiliation: New Jersey Medical School, Rutgers University , Newark, NJ, USA.

ABSTRACT
Mesenchymal stem cells (MSCs) are promising cellular suppressor of inflammation. This function of MSCs is partly due to their licensing by inflammatory mediators. In cases with reduced inflammation, MSCs could become immune-enhancer cells. MSCs can suppress the inflammatory response of antigen-challenged lymphocytes from allergic asthma. Although allergic rhinitis (AR) is also an inflammatory response, it is unclear if MSCs can exert similar suppression. This study investigated the immune effects (suppressor vs enhancer) of MSCs on allergen-stimulated lymphocytes from AR subjects (grass or weed allergy). In contrast to subjects with allergic asthma, MSCs caused a significant (P<0.05) increase in the proliferation of antigen-challenged lymphocytes from AR subjects. The increase in lymphocyte proliferation was caused by the MSCs presenting the allergens to CD4(+) T cells (antigen-presenting cells (APCs)). This correlated with increased production of inflammatory cytokines from T cells, and increased expressions of major histocompatibility complex (MHC)-II and CD86 on MSCs. The specificity of APC function was demonstrated in APC assay using MSCs that were knocked down for the master regulator of MHC-II transcription, CIITA. The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests. Thus, we deduced that the contrasting immune effects of MSCs for antigen-challenged lymphocytes on AR and allergic asthma could be disease specific. It is possible that the enhanced inflammation from asthma might be required to license the MSCs to become suppressor cells. This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

No MeSH data available.


Related in: MedlinePlus

Proliferation of peripheral blood mononuclear cells (PBMCs) from allergic (ragweed) asthma, in the presence or absence of mesenchymal stem cells (MSCs). PBMCs from subjects with allergy to ragweed and asthma (allergic asthma) were stimulated with ragweed (5 μl ml−1), in the presence or absence of MSCs. After 48 h, the cultures were assessed for proliferation by pulsing with tritiated thymidine. The incorporation of tritiated thymidine was detected with a scintillation counter. The proliferation for each experimental point is presented as stimulation index (SI), which was calculated as the disintegration per minute (d.p.m.) of the experimental point/d.p.m. of PBMCs alone. The results (mean±s.d.) are presented for four donors (Table 1: S18–S21). Each donor was studied in quadruplicates, with MSCs from a different donor.
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fig3: Proliferation of peripheral blood mononuclear cells (PBMCs) from allergic (ragweed) asthma, in the presence or absence of mesenchymal stem cells (MSCs). PBMCs from subjects with allergy to ragweed and asthma (allergic asthma) were stimulated with ragweed (5 μl ml−1), in the presence or absence of MSCs. After 48 h, the cultures were assessed for proliferation by pulsing with tritiated thymidine. The incorporation of tritiated thymidine was detected with a scintillation counter. The proliferation for each experimental point is presented as stimulation index (SI), which was calculated as the disintegration per minute (d.p.m.) of the experimental point/d.p.m. of PBMCs alone. The results (mean±s.d.) are presented for four donors (Table 1: S18–S21). Each donor was studied in quadruplicates, with MSCs from a different donor.

Mentions: The low expression of MHC-II on MSCs are sufficient to elicit allogeneic responses.22 To account for the contribution of allogeneic differences between the MSCs and the test PBMCs, all of the studies included controls consisting of one-way mixed reactions with MSCs as stimulators and PBMCs as responders (Figures 1, 2, 3, open bars). Studies with γ-irradiated MSCs (2000 Rads) vs non-irradiated MSCs confirmed that the proliferation observed in the mixed cultures was indeed due solely to the PBMCs and not the MSCs (Supplementary Figure S1 online).


Pollen-induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis.

Desai MB, Gavrilova T, Liu J, Patel SA, Kartan S, Greco SJ, Capitle E, Rameshwar P - Clin Transl Immunology (2013)

Proliferation of peripheral blood mononuclear cells (PBMCs) from allergic (ragweed) asthma, in the presence or absence of mesenchymal stem cells (MSCs). PBMCs from subjects with allergy to ragweed and asthma (allergic asthma) were stimulated with ragweed (5 μl ml−1), in the presence or absence of MSCs. After 48 h, the cultures were assessed for proliferation by pulsing with tritiated thymidine. The incorporation of tritiated thymidine was detected with a scintillation counter. The proliferation for each experimental point is presented as stimulation index (SI), which was calculated as the disintegration per minute (d.p.m.) of the experimental point/d.p.m. of PBMCs alone. The results (mean±s.d.) are presented for four donors (Table 1: S18–S21). Each donor was studied in quadruplicates, with MSCs from a different donor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232057&req=5

fig3: Proliferation of peripheral blood mononuclear cells (PBMCs) from allergic (ragweed) asthma, in the presence or absence of mesenchymal stem cells (MSCs). PBMCs from subjects with allergy to ragweed and asthma (allergic asthma) were stimulated with ragweed (5 μl ml−1), in the presence or absence of MSCs. After 48 h, the cultures were assessed for proliferation by pulsing with tritiated thymidine. The incorporation of tritiated thymidine was detected with a scintillation counter. The proliferation for each experimental point is presented as stimulation index (SI), which was calculated as the disintegration per minute (d.p.m.) of the experimental point/d.p.m. of PBMCs alone. The results (mean±s.d.) are presented for four donors (Table 1: S18–S21). Each donor was studied in quadruplicates, with MSCs from a different donor.
Mentions: The low expression of MHC-II on MSCs are sufficient to elicit allogeneic responses.22 To account for the contribution of allogeneic differences between the MSCs and the test PBMCs, all of the studies included controls consisting of one-way mixed reactions with MSCs as stimulators and PBMCs as responders (Figures 1, 2, 3, open bars). Studies with γ-irradiated MSCs (2000 Rads) vs non-irradiated MSCs confirmed that the proliferation observed in the mixed cultures was indeed due solely to the PBMCs and not the MSCs (Supplementary Figure S1 online).

Bottom Line: In cases with reduced inflammation, MSCs could become immune-enhancer cells.The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests.This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

View Article: PubMed Central - PubMed

Affiliation: New Jersey Medical School, Rutgers University , Newark, NJ, USA.

ABSTRACT
Mesenchymal stem cells (MSCs) are promising cellular suppressor of inflammation. This function of MSCs is partly due to their licensing by inflammatory mediators. In cases with reduced inflammation, MSCs could become immune-enhancer cells. MSCs can suppress the inflammatory response of antigen-challenged lymphocytes from allergic asthma. Although allergic rhinitis (AR) is also an inflammatory response, it is unclear if MSCs can exert similar suppression. This study investigated the immune effects (suppressor vs enhancer) of MSCs on allergen-stimulated lymphocytes from AR subjects (grass or weed allergy). In contrast to subjects with allergic asthma, MSCs caused a significant (P<0.05) increase in the proliferation of antigen-challenged lymphocytes from AR subjects. The increase in lymphocyte proliferation was caused by the MSCs presenting the allergens to CD4(+) T cells (antigen-presenting cells (APCs)). This correlated with increased production of inflammatory cytokines from T cells, and increased expressions of major histocompatibility complex (MHC)-II and CD86 on MSCs. The specificity of APC function was demonstrated in APC assay using MSCs that were knocked down for the master regulator of MHC-II transcription, CIITA. The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests. Thus, we deduced that the contrasting immune effects of MSCs for antigen-challenged lymphocytes on AR and allergic asthma could be disease specific. It is possible that the enhanced inflammation from asthma might be required to license the MSCs to become suppressor cells. This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

No MeSH data available.


Related in: MedlinePlus