CD4 T-cell subsets in Malaria: TH1/TH2 revisited
CD4+ T cells have been shown to play a central role in immune control of infection with Plasmodium parasites. At the erythrocytic stage of infection, IFN-γ production by CD4+ T cells and CD4+ T-cell help for the B-cell response are required for control and elimination of infected red blood cells. C...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00671/full |
| _version_ | 1818127423469780992 |
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| author | Damian ePerez-Mazliah Jean eLanghorne |
| author_facet | Damian ePerez-Mazliah Jean eLanghorne |
| author_sort | Damian ePerez-Mazliah |
| collection | DOAJ |
| description | CD4+ T cells have been shown to play a central role in immune control of infection with Plasmodium parasites. At the erythrocytic stage of infection, IFN-γ production by CD4+ T cells and CD4+ T-cell help for the B-cell response are required for control and elimination of infected red blood cells. CD4+ T cells are also important for controlling Plasmodium pre-erythrocytic stages through the activation of parasite-specific CD8+ T cells. However, excessive inflammatory responses triggered by the infection have been shown to drive pathology. Early classical experiments demonstrated a biphasic CD4+ T-cell response against erythrocytic stages in mice, in which T helper (Th)1 and antibody helper CD4+ T cells appear sequentially during a primary infection. While IFN-γ-producing Th1 cells do play a role in controlling acute infections, and they contribute to acute erythrocytic-stage pathology, it became apparent that a classical Th2 response producing IL-4 is not a critical feature of the CD4+ T cell response during the chronic phase of infection. Rather, effective CD4+ T-cell help for B cells, which can occur in the absence of IL-4, is required to control chronic parasitemia. IL-10, important to counterbalance inflammation and associated with protection from inflammatory-mediated severe malaria in both humans and experimental models, was originally considered be produced by CD4+ Th2 cells during infection. We review the interpretations of CD4+ T cell responses during Plasmodium infection, proposed under the original Th1/Th2 paradigm, in light of more recent advances, including the identification of multifunctional T cells such as Th1 cells co-expressing IFN-γ and IL-10, the identification of follicular helper T cells (Tfh) as the predominant CD4+ T helper subset for B cells, and the recognition of inherent plasticity in the fates of different CD4+ T cells. |
| first_indexed | 2024-12-11T07:17:07Z |
| format | Article |
| id | doaj.art-5efd3a59cb5949ff96f9f0424d9f8dd5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T07:17:07Z |
| publishDate | 2015-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5efd3a59cb5949ff96f9f0424d9f8dd52022-12-22T01:16:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-01-01510.3389/fimmu.2014.00671117648CD4 T-cell subsets in Malaria: TH1/TH2 revisitedDamian ePerez-Mazliah0Jean eLanghorne1MRC National Institute for Medical ResearchMRC National Institute for Medical ResearchCD4+ T cells have been shown to play a central role in immune control of infection with Plasmodium parasites. At the erythrocytic stage of infection, IFN-γ production by CD4+ T cells and CD4+ T-cell help for the B-cell response are required for control and elimination of infected red blood cells. CD4+ T cells are also important for controlling Plasmodium pre-erythrocytic stages through the activation of parasite-specific CD8+ T cells. However, excessive inflammatory responses triggered by the infection have been shown to drive pathology. Early classical experiments demonstrated a biphasic CD4+ T-cell response against erythrocytic stages in mice, in which T helper (Th)1 and antibody helper CD4+ T cells appear sequentially during a primary infection. While IFN-γ-producing Th1 cells do play a role in controlling acute infections, and they contribute to acute erythrocytic-stage pathology, it became apparent that a classical Th2 response producing IL-4 is not a critical feature of the CD4+ T cell response during the chronic phase of infection. Rather, effective CD4+ T-cell help for B cells, which can occur in the absence of IL-4, is required to control chronic parasitemia. IL-10, important to counterbalance inflammation and associated with protection from inflammatory-mediated severe malaria in both humans and experimental models, was originally considered be produced by CD4+ Th2 cells during infection. We review the interpretations of CD4+ T cell responses during Plasmodium infection, proposed under the original Th1/Th2 paradigm, in light of more recent advances, including the identification of multifunctional T cells such as Th1 cells co-expressing IFN-γ and IL-10, the identification of follicular helper T cells (Tfh) as the predominant CD4+ T helper subset for B cells, and the recognition of inherent plasticity in the fates of different CD4+ T cells.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00671/fullMalariaPlasmodiumTh1th2Th22Tfh cells |
| spellingShingle | Damian ePerez-Mazliah Jean eLanghorne CD4 T-cell subsets in Malaria: TH1/TH2 revisited Frontiers in Immunology Malaria Plasmodium Th1 th2 Th22 Tfh cells |
| title | CD4 T-cell subsets in Malaria: TH1/TH2 revisited |
| title_full | CD4 T-cell subsets in Malaria: TH1/TH2 revisited |
| title_fullStr | CD4 T-cell subsets in Malaria: TH1/TH2 revisited |
| title_full_unstemmed | CD4 T-cell subsets in Malaria: TH1/TH2 revisited |
| title_short | CD4 T-cell subsets in Malaria: TH1/TH2 revisited |
| title_sort | cd4 t cell subsets in malaria th1 th2 revisited |
| topic | Malaria Plasmodium Th1 th2 Th22 Tfh cells |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00671/full |
| work_keys_str_mv | AT damianeperezmazliah cd4tcellsubsetsinmalariath1th2revisited AT jeanelanghorne cd4tcellsubsetsinmalariath1th2revisited |