Cytotoxic human CD4+ T cells

Berg, Pablo J van de; Leeuwen, Eveline van; Berge, Ineke J. ten; Lier, R. A. W. Van

doi:10.1016/j.coi.2008.03.007

Cited by 113 publications

(97 citation statements)

References 71 publications

(62 reference statements)

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“…More recently, a direct role for CD4 T cells has been suggested in chronic infections, such as cytomegalovirus (CMV), EpsteinBarr virus, and HIV infections in humans (43) and gammaherpesvirus infections in mice (35). These data indicate that chronic antigen exposure induces a highly differentiated CD4 T cell effector with cytolytic potential (1).…”

mentioning

confidence: 69%

Multifunctional CD4 Cells Expressing Gamma Interferon and Perforin Mediate Protection against Lethal Influenza Virus Infection

Brown

Lee

García-Hernández

et al. 2012

J Virol

221

239

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CD4 effectors generated in vitro can promote survival against a highly pathogenic influenza virus via an antibody-independent mechanism involving class II-restricted, perforin-mediated cytotoxicity. However, it is not known whether CD4 cells activated during influenza virus infection can acquire cytolytic activity that contributes to protection against lethal challenge. CD4 cells isolated from the lungs of infected mice were able to confer protection against a lethal dose of H1N1 influenza virus A/Puerto Rico 8/34 (PR8). Infection of BALB/c mice with PR8 induced a multifunctional CD4 population with proliferative capacity and ability to secrete interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α) in the draining lymph node (DLN) and gamma interferon (IFN-γ) and IL-10 in the lung. IFN-γ-deficient CD4 cells produced larger amounts of IL-17 and similar levels of TNF-α, IL-10, and IL-2 compared to wild-type (WT) CD4 cells. Both WT and IFN-γ −/− CD4 cells exhibit influenza virus-specific cytotoxicity; however, IFN-γ-deficient CD4 cells did not promote recovery after lethal infection as effectively as WT CD4 cells. PR8 infection induced a population of cytolytic CD4 effectors that resided in the lung but not the DLN. These cells expressed granzyme B (GrB) and required perforin to lyse peptide-pulsed targets. Lethally infected mice given influenza virus-specific CD4 cells deficient in perforin showed greater weight loss and a slower time to recovery than mice given WT influenza virus-specific CD4 cells. Taken together, these data strengthen the concept that CD4 T cell effectors are broadly multifunctional with direct roles in promoting protection against lethal influenza virus infection.

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mentioning

confidence: 69%

Multifunctional CD4 Cells Expressing Gamma Interferon and Perforin Mediate Protection against Lethal Influenza Virus Infection

Brown

Lee

García-Hernández

et al. 2012

J Virol

221

239

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“…Although tumor-specific CD8 + T cells are still considered the mainstream effector component of adoptive immunotherapy (42,43), several in vitro findings have clearly pointed out that CD4 + T cells are also endowed with Ag-specific lytic activity (18,44) and therefore could per se be capable of effector functions. In EBV-related malignancies, virus-specific clonal or polyclonal lytic CD4 + T cell lines can block LCL proliferation and growth in vitro (17,45).…”

Section: Discussionmentioning

confidence: 99%

Virus-Specific Cytotoxic CD4+ T Cells for the Treatment of EBV-Related Tumors

Merlo

Turrini

Bobisse

et al. 2010

The Journal of Immunology

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“…These cells were found to be MHC class IIrestricted cytotoxic T-cells. 41,42 Cassaza 22 reported their ability to kill CMV Ag-loaded B-LCLs.…”

Section: Discussionmentioning

confidence: 99%

Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT

Krol

Stuchlý

Hubáček

et al. 2010

Bone Marrow Transplant

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Depletion of cellular immunity as a consequence of conditioning before allogeneic hematopoietic SCT (HSCT) frequently results in CMV reactivation, which may in turn lead to life-threatening infections and require timely antiviral treatment. We have investigated the functional signatures of CMV-specific CD4 þ and CD8 þ T-cells in 191 samples from 118 individuals. We compared healthy donors with both patients with high and undetectable viral loads, and those who controlled and did not control their CMV reactivations. Polychromatic flowcytometric measurements of CD154 (CD40L), intracellular cytokines (IFNc, IL2) and a degranulation marker (CD107a) allowed us to assess the functional status of various T-cells simultaneously. We found that dual IFNc/ IL2-producing CD8 þ T-cells were present in patients controlling their CMV reactivations but absent from noncontrollers. CD8 þ T-cells that produce only IFNc were the most abundant subtype, but they most likely represent non-protective memory cells. Distinct functional signatures were examined by hierarchical clustering, and this revealed that, unlike polyfunctional CD8 þ T-cells, CD8 þ T-cells that produce IFNc alone were not functioning in concert with other subsets. In conclusion, our study revealed functional signatures that may be useful for immune monitoring, and it could change the interpretation of previous studies that assessed only IFNc.

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Cytotoxic human CD4+ T cells

Cited by 113 publications

References 71 publications

Multifunctional CD4 Cells Expressing Gamma Interferon and Perforin Mediate Protection against Lethal Influenza Virus Infection

Multifunctional CD4 Cells Expressing Gamma Interferon and Perforin Mediate Protection against Lethal Influenza Virus Infection

Virus-Specific Cytotoxic CD4+ T Cells for the Treatment of EBV-Related Tumors

Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT

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