Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children

Ricardo da Silva Antunes; Aaron Sutherland; April Frazier; Veronique Schulten; Anna Pomés; Jill Glesner; Agustin Calatroni; Matthew C. Altman; Robert A. Wood; George T. O'Connor; Jacqueline A. Pongracic; Gurjit K. Khurana Hershey; Carolyn M. Kercsmar; Rebecca S. Gruchalla; Michelle Gill; Andrew H. Liu; Edward Zoratti; Meyer Kattan; Paula J. Busse; Leonard B. Bacharier; Stephen J. Teach; Lisa M. Wheatley; Alkis Togias; William W. Busse; Daniel J. Jackson; Alessandro Sette

doi:10.1002/clt2.12073

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children

Ricardo da Silva Antunes, Aaron Sutherland, April Frazier, Veronique Schulten, Anna Pomés, Jill Glesner, Agustin Calatroni, Matthew C. Altman, Robert A. Wood, George T. O'Connor, Jacqueline A. Pongracic, Gurjit K. Khurana Hershey, Carolyn M. Kercsmar, Rebecca S. Gruchalla, Michelle Gill, Andrew H. Liu, Edward Zoratti, Meyer Kattan, Paula J. Busse, Leonard B. BacharierStephen J. Teach, Lisa M. Wheatley, Alkis Togias, William W. Busse, Daniel J. Jackson, Alessandro Sette^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

Original language	English (US)
Article number	e12073
Journal	Clinical and Translational Allergy
Volume	11
Issue number	8
DOIs	https://doi.org/10.1002/clt2.12073
State	Published - Oct 2021

Funding

We wish to acknowledge all subjects for their participation and donate their blood and time for this study. The authors wish to thank all the personnel from the clinical sites involved in this work and Rho, particularly Amanda Farrell, Stephanie Wellford, Jessica Baucom, and Kelly Penke for their incessant efforts, supervision, and coordination. This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grants 1UM1AI114271‐01, UM2AI117870, and 5UM1AI114271‐03. Additional support was provided by the National Center for Research Resources, and National Center for Advancing Translational Sciences, National Institutes of Health, under grants NCATS/NIH UL1TR001079, NCATS/NIH UL1TR001422, NCATS/NIH UL1TR001876, NIH/CTSA 5UL1TR001425‐03, and NIAID/NIH U19AI135731. Dr. Lisa M. Wheatley and Alkis Togias co‐authorship of this publication does not necessarily constitute endorsement by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health or any other agency of the United States government. We wish to acknowledge all subjects for their participation and donate their blood and time for this study. The authors wish to thank all the personnel from the clinical sites involved in this work and Rho, particularly Amanda Farrell, Stephanie Wellford, Jessica Baucom, and Kelly Penke for their incessant efforts, supervision, and coordination. This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grants 1UM1AI114271-01, UM2AI117870, and 5UM1AI114271-03. Additional support was provided by the National Center for Research Resources, and National Center for Advancing Translational Sciences, National Institutes of Health, under grants NCATS/NIH UL1TR001079, NCATS/NIH UL1TR001422, NCATS/NIH UL1TR001876, NIH/CTSA 5UL1TR001425-03, and NIAID/NIH U19AI135731. Dr. Lisa M. Wheatley and Alkis Togias co-authorship of this publication does not necessarily constitute endorsement by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health or any other agency of the United States government.

Keywords

T cell
allergens
asthma
clinical immunology
cockroach

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Immunology and Allergy
Immunology

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10.1002/clt2.12073

Cite this

da Silva Antunes, R., Sutherland, A., Frazier, A., Schulten, V., Pomés, A., Glesner, J., Calatroni, A., Altman, M. C., Wood, R. A., O'Connor, G. T., Pongracic, J. A., Khurana Hershey, G. K., Kercsmar, C. M., Gruchalla, R. S., Gill, M., Liu, A. H., Zoratti, E., Kattan, M., Busse, P. J., ... Sette, A. (2021). Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children. Clinical and Translational Allergy, 11(8), Article e12073. https://doi.org/10.1002/clt2.12073

@article{af009f25a671472b87854114ff83cdf8,

title = "Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children",

abstract = "Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.",

keywords = "T cell, allergens, asthma, clinical immunology, cockroach",

author = "{da Silva Antunes}, Ricardo and Aaron Sutherland and April Frazier and Veronique Schulten and Anna Pom{\'e}s and Jill Glesner and Agustin Calatroni and Altman, {Matthew C.} and Wood, {Robert A.} and O'Connor, {George T.} and Pongracic, {Jacqueline A.} and {Khurana Hershey}, {Gurjit K.} and Kercsmar, {Carolyn M.} and Gruchalla, {Rebecca S.} and Michelle Gill and Liu, {Andrew H.} and Edward Zoratti and Meyer Kattan and Busse, {Paula J.} and Bacharier, {Leonard B.} and Teach, {Stephen J.} and Wheatley, {Lisa M.} and Alkis Togias and Busse, {William W.} and Jackson, {Daniel J.} and Alessandro Sette",

note = "Funding Information: We wish to acknowledge all subjects for their participation and donate their blood and time for this study. The authors wish to thank all the personnel from the clinical sites involved in this work and Rho, particularly Amanda Farrell, Stephanie Wellford, Jessica Baucom, and Kelly Penke for their incessant efforts, supervision, and coordination. This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grants 1UM1AI114271‐01, UM2AI117870, and 5UM1AI114271‐03. Additional support was provided by the National Center for Research Resources, and National Center for Advancing Translational Sciences, National Institutes of Health, under grants NCATS/NIH UL1TR001079, NCATS/NIH UL1TR001422, NCATS/NIH UL1TR001876, NIH/CTSA 5UL1TR001425‐03, and NIAID/NIH U19AI135731. Dr. Lisa M. Wheatley and Alkis Togias co‐authorship of this publication does not necessarily constitute endorsement by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health or any other agency of the United States government. Funding Information: We wish to acknowledge all subjects for their participation and donate their blood and time for this study. The authors wish to thank all the personnel from the clinical sites involved in this work and Rho, particularly Amanda Farrell, Stephanie Wellford, Jessica Baucom, and Kelly Penke for their incessant efforts, supervision, and coordination. This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grants 1UM1AI114271-01, UM2AI117870, and 5UM1AI114271-03. Additional support was provided by the National Center for Research Resources, and National Center for Advancing Translational Sciences, National Institutes of Health, under grants NCATS/NIH UL1TR001079, NCATS/NIH UL1TR001422, NCATS/NIH UL1TR001876, NIH/CTSA 5UL1TR001425-03, and NIAID/NIH U19AI135731. Dr. Lisa M. Wheatley and Alkis Togias co-authorship of this publication does not necessarily constitute endorsement by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health or any other agency of the United States government. Publisher Copyright: {\textcopyright} 2021 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.",

year = "2021",

month = oct,

doi = "10.1002/clt2.12073",

language = "English (US)",

volume = "11",

journal = "Clinical and Translational Allergy",

issn = "2045-7022",

publisher = "BioMed Central",

number = "8",

}

da Silva Antunes, R, Sutherland, A, Frazier, A, Schulten, V, Pomés, A, Glesner, J, Calatroni, A, Altman, MC, Wood, RA, O'Connor, GT, Pongracic, JA, Khurana Hershey, GK, Kercsmar, CM, Gruchalla, RS, Gill, M, Liu, AH, Zoratti, E, Kattan, M, Busse, PJ, Bacharier, LB, Teach, SJ, Wheatley, LM, Togias, A, Busse, WW, Jackson, DJ & Sette, A 2021, 'Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children', Clinical and Translational Allergy, vol. 11, no. 8, e12073. https://doi.org/10.1002/clt2.12073

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children. / da Silva Antunes, Ricardo; Sutherland, Aaron; Frazier, April et al.
In: Clinical and Translational Allergy, Vol. 11, No. 8, e12073, 10.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children

AU - da Silva Antunes, Ricardo

AU - Sutherland, Aaron

AU - Frazier, April

AU - Schulten, Veronique

AU - Pomés, Anna

AU - Glesner, Jill

AU - Calatroni, Agustin

AU - Altman, Matthew C.

AU - Wood, Robert A.

AU - O'Connor, George T.

AU - Pongracic, Jacqueline A.

AU - Khurana Hershey, Gurjit K.

AU - Kercsmar, Carolyn M.

AU - Gruchalla, Rebecca S.

AU - Gill, Michelle

AU - Liu, Andrew H.

AU - Zoratti, Edward

AU - Kattan, Meyer

AU - Busse, Paula J.

AU - Bacharier, Leonard B.

AU - Teach, Stephen J.

AU - Wheatley, Lisa M.

AU - Togias, Alkis

AU - Busse, William W.

AU - Jackson, Daniel J.

AU - Sette, Alessandro

N1 - Funding Information: We wish to acknowledge all subjects for their participation and donate their blood and time for this study. The authors wish to thank all the personnel from the clinical sites involved in this work and Rho, particularly Amanda Farrell, Stephanie Wellford, Jessica Baucom, and Kelly Penke for their incessant efforts, supervision, and coordination. This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grants 1UM1AI114271‐01, UM2AI117870, and 5UM1AI114271‐03. Additional support was provided by the National Center for Research Resources, and National Center for Advancing Translational Sciences, National Institutes of Health, under grants NCATS/NIH UL1TR001079, NCATS/NIH UL1TR001422, NCATS/NIH UL1TR001876, NIH/CTSA 5UL1TR001425‐03, and NIAID/NIH U19AI135731. Dr. Lisa M. Wheatley and Alkis Togias co‐authorship of this publication does not necessarily constitute endorsement by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health or any other agency of the United States government. Funding Information: We wish to acknowledge all subjects for their participation and donate their blood and time for this study. The authors wish to thank all the personnel from the clinical sites involved in this work and Rho, particularly Amanda Farrell, Stephanie Wellford, Jessica Baucom, and Kelly Penke for their incessant efforts, supervision, and coordination. This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grants 1UM1AI114271-01, UM2AI117870, and 5UM1AI114271-03. Additional support was provided by the National Center for Research Resources, and National Center for Advancing Translational Sciences, National Institutes of Health, under grants NCATS/NIH UL1TR001079, NCATS/NIH UL1TR001422, NCATS/NIH UL1TR001876, NIH/CTSA 5UL1TR001425-03, and NIAID/NIH U19AI135731. Dr. Lisa M. Wheatley and Alkis Togias co-authorship of this publication does not necessarily constitute endorsement by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health or any other agency of the United States government. Publisher Copyright: © 2021 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

PY - 2021/10

Y1 - 2021/10

N2 - Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

AB - Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

KW - T cell

KW - allergens

KW - asthma

KW - clinical immunology

KW - cockroach

UR - http://www.scopus.com/inward/record.url?scp=85117914921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85117914921&partnerID=8YFLogxK

U2 - 10.1002/clt2.12073

DO - 10.1002/clt2.12073

M3 - Article

C2 - 34691392

AN - SCOPUS:85117914921

SN - 2045-7022

VL - 11

JO - Clinical and Translational Allergy

JF - Clinical and Translational Allergy

IS - 8

M1 - e12073

ER -

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children

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