title: T-bet modulates the antibody response and immune protection during murine malaria.
abstract: CD4(+) T-cell subtypes govern the synthesis of different Ab isotypes and other immune functions. The influence of CD4(+) T-cell differentiation programs on isotype switching and other aspects of host immunological networks during malaria infection are currently poorly understood. Here, we used Tbx21(-/-) mice deficient for T-bet, a regulator of Th1 CD4(+) T-cell differentiation, to examine the effect of Th1 CD4(+) T cells on the immune protection to nonlethal murine malaria Plasmodium yoelii 17XNL. We found that Tbx21(-/-) mice exhibited significantly lower parasite burden that correlated with elevated levels of IgG1, indicating that T-bet-dependent Ab isotype switching may be responsible for lower parasite burden. Absence of T-bet was also associated with a transient but significant loss of T cells during the infection, suggesting that T-bet may suppress malaria-induced apoptosis or induce proliferation of T cells. However, Tbx21(-/-) mice produced greater numbers of Foxp3(+) CD25(+) regulatory CD4(+) T cells, which may contribute to the early contraction of T cells. Lastly, Tbx21(-/-) mice exhibited unimpaired production of IFN-γ by a diverse repertoire of immune cell subsets and a selective expansion of IFN-γ-producing T cells. These observations may have implications in malaria vaccine design.
authors.affiliation: Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, MD, USA.
authors.forename: Miranda S
authors.initials: MS
authors.lastname: Oakley
authors.forename: Bikash R
authors.initials: BR
authors.lastname: Sahu
authors.forename: Leda
authors.initials: L
authors.lastname: Lotspeich-Cole
authors.forename: Victoria
authors.initials: V
authors.lastname: Majam
authors.forename: Phuong
authors.initials: P
authors.lastname: Thao Pham
authors.forename: Aditi
authors.initials: A
authors.lastname: Sengupta Banerjee
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kozakai
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Morris
authors.forename: Sanjai
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000917:Antibody Formation; D017578:Immunoglobulin Class Switching; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010967:Plasmodium yoelii / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma
keywords: IgG1; Immunity; Plasmodium yoelii; T-bet