HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria

Wathsala Wijayalath, Rebecca Danner, Yuliya Kleschenko, Sai Majji, Eileen Franke Villasante, Thomas L. Richie, Teodor Doru Brumeanu, Chella S. David, Sofia Casares

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Unlike human malaria parasites that induce persistent infection, some rodent malaria parasites, like Plasmodium yoelii strain 17XNL (Py17XNL), induce a transient (self-curing) malaria infection. Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells. In order to better understand the correspondence between murine malaria models and human malaria, and in particular the role of MHC (HLA) class II molecules, we studied the ability of humanized mice expressing human HLA class II molecules to clear Py17XNL infection. We showed that humanized mice expressing HLA-DR4 (DR0401) molecules and lacking mouse MHC class II molecules (EA0) have impaired production of specific antibodies to Py17XNL and cannot cure the infection. In contrast, mice expressing HLA-DR4 (DR0402), HLA-DQ6 (DQ0601), HLA-DQ8 (DQ0302), or HLA-DR3 (DR0301) molecules in an EA0 background were able to elicit specific antibodies and self-cure the infection. In a series of experiments, we determined that the inability of humanized DR0401.EA0 mice to elicit specific antibodies was due to expansion and activation of regulatory CD4+ Foxp3+ T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions. Treg depletion allowed the DR0401.EA0 mice to elicit specific antibodies and self-cure the infection. Our results demonstrated a differential role of MHC (HLA) class II molecules in supporting antibody responses to Py17XNL malaria and revealed a new mechanism by which malaria parasites stimulate B cell-suppressogenic Tregs that prevent clearance of infection.

Original languageEnglish (US)
Pages (from-to)286-297
Number of pages12
JournalInfection and Immunity
Volume82
Issue number1
DOIs
StatePublished - Jan 2014

Fingerprint

Plasmodium yoelii
Regulatory T-Lymphocytes
Malaria
B-Lymphocytes
Major Histocompatibility Complex
Infection
Parasites
Antibodies
HLA-DR4 Antigen
T-Lymphocytes
Antibody Formation
HLA-DR3 Antigen
Cell Communication
Rodentia

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Wijayalath, W., Danner, R., Kleschenko, Y., Majji, S., Villasante, E. F., Richie, T. L., ... Casares, S. (2014). HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria. Infection and Immunity, 82(1), 286-297. https://doi.org/10.1128/IAI.00272-13

HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria. / Wijayalath, Wathsala; Danner, Rebecca; Kleschenko, Yuliya; Majji, Sai; Villasante, Eileen Franke; Richie, Thomas L.; Brumeanu, Teodor Doru; David, Chella S.; Casares, Sofia.

In: Infection and Immunity, Vol. 82, No. 1, 01.2014, p. 286-297.

Research output: Contribution to journalArticle

Wijayalath, W, Danner, R, Kleschenko, Y, Majji, S, Villasante, EF, Richie, TL, Brumeanu, TD, David, CS & Casares, S 2014, 'HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria', Infection and Immunity, vol. 82, no. 1, pp. 286-297. https://doi.org/10.1128/IAI.00272-13
Wijayalath, Wathsala ; Danner, Rebecca ; Kleschenko, Yuliya ; Majji, Sai ; Villasante, Eileen Franke ; Richie, Thomas L. ; Brumeanu, Teodor Doru ; David, Chella S. ; Casares, Sofia. / HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria. In: Infection and Immunity. 2014 ; Vol. 82, No. 1. pp. 286-297.
@article{3acde2c2b1f944b49589fec45243b7ad,
title = "HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria",
abstract = "Unlike human malaria parasites that induce persistent infection, some rodent malaria parasites, like Plasmodium yoelii strain 17XNL (Py17XNL), induce a transient (self-curing) malaria infection. Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells. In order to better understand the correspondence between murine malaria models and human malaria, and in particular the role of MHC (HLA) class II molecules, we studied the ability of humanized mice expressing human HLA class II molecules to clear Py17XNL infection. We showed that humanized mice expressing HLA-DR4 (DR0401) molecules and lacking mouse MHC class II molecules (EA0) have impaired production of specific antibodies to Py17XNL and cannot cure the infection. In contrast, mice expressing HLA-DR4 (DR0402), HLA-DQ6 (DQ0601), HLA-DQ8 (DQ0302), or HLA-DR3 (DR0301) molecules in an EA0 background were able to elicit specific antibodies and self-cure the infection. In a series of experiments, we determined that the inability of humanized DR0401.EA0 mice to elicit specific antibodies was due to expansion and activation of regulatory CD4+ Foxp3+ T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions. Treg depletion allowed the DR0401.EA0 mice to elicit specific antibodies and self-cure the infection. Our results demonstrated a differential role of MHC (HLA) class II molecules in supporting antibody responses to Py17XNL malaria and revealed a new mechanism by which malaria parasites stimulate B cell-suppressogenic Tregs that prevent clearance of infection.",
author = "Wathsala Wijayalath and Rebecca Danner and Yuliya Kleschenko and Sai Majji and Villasante, {Eileen Franke} and Richie, {Thomas L.} and Brumeanu, {Teodor Doru} and David, {Chella S.} and Sofia Casares",
year = "2014",
month = "1",
doi = "10.1128/IAI.00272-13",
language = "English (US)",
volume = "82",
pages = "286--297",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "1",

}

TY - JOUR

T1 - HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria

AU - Wijayalath, Wathsala

AU - Danner, Rebecca

AU - Kleschenko, Yuliya

AU - Majji, Sai

AU - Villasante, Eileen Franke

AU - Richie, Thomas L.

AU - Brumeanu, Teodor Doru

AU - David, Chella S.

AU - Casares, Sofia

PY - 2014/1

Y1 - 2014/1

N2 - Unlike human malaria parasites that induce persistent infection, some rodent malaria parasites, like Plasmodium yoelii strain 17XNL (Py17XNL), induce a transient (self-curing) malaria infection. Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells. In order to better understand the correspondence between murine malaria models and human malaria, and in particular the role of MHC (HLA) class II molecules, we studied the ability of humanized mice expressing human HLA class II molecules to clear Py17XNL infection. We showed that humanized mice expressing HLA-DR4 (DR0401) molecules and lacking mouse MHC class II molecules (EA0) have impaired production of specific antibodies to Py17XNL and cannot cure the infection. In contrast, mice expressing HLA-DR4 (DR0402), HLA-DQ6 (DQ0601), HLA-DQ8 (DQ0302), or HLA-DR3 (DR0301) molecules in an EA0 background were able to elicit specific antibodies and self-cure the infection. In a series of experiments, we determined that the inability of humanized DR0401.EA0 mice to elicit specific antibodies was due to expansion and activation of regulatory CD4+ Foxp3+ T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions. Treg depletion allowed the DR0401.EA0 mice to elicit specific antibodies and self-cure the infection. Our results demonstrated a differential role of MHC (HLA) class II molecules in supporting antibody responses to Py17XNL malaria and revealed a new mechanism by which malaria parasites stimulate B cell-suppressogenic Tregs that prevent clearance of infection.

AB - Unlike human malaria parasites that induce persistent infection, some rodent malaria parasites, like Plasmodium yoelii strain 17XNL (Py17XNL), induce a transient (self-curing) malaria infection. Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells. In order to better understand the correspondence between murine malaria models and human malaria, and in particular the role of MHC (HLA) class II molecules, we studied the ability of humanized mice expressing human HLA class II molecules to clear Py17XNL infection. We showed that humanized mice expressing HLA-DR4 (DR0401) molecules and lacking mouse MHC class II molecules (EA0) have impaired production of specific antibodies to Py17XNL and cannot cure the infection. In contrast, mice expressing HLA-DR4 (DR0402), HLA-DQ6 (DQ0601), HLA-DQ8 (DQ0302), or HLA-DR3 (DR0301) molecules in an EA0 background were able to elicit specific antibodies and self-cure the infection. In a series of experiments, we determined that the inability of humanized DR0401.EA0 mice to elicit specific antibodies was due to expansion and activation of regulatory CD4+ Foxp3+ T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions. Treg depletion allowed the DR0401.EA0 mice to elicit specific antibodies and self-cure the infection. Our results demonstrated a differential role of MHC (HLA) class II molecules in supporting antibody responses to Py17XNL malaria and revealed a new mechanism by which malaria parasites stimulate B cell-suppressogenic Tregs that prevent clearance of infection.

UR - http://www.scopus.com/inward/record.url?scp=84890820495&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890820495&partnerID=8YFLogxK

U2 - 10.1128/IAI.00272-13

DO - 10.1128/IAI.00272-13

M3 - Article

VL - 82

SP - 286

EP - 297

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 1

ER -