T cell help in human antigen-specific antibody responses can be replaced by interleukin 2

1986 ◽  
Vol 16 (9) ◽  
pp. 1037-1042 ◽  
Author(s):  
Robin E. Callard ◽  
Susan H. Smith ◽  
John G. Shields ◽  
Roland J. Levinsky
Keyword(s):  
T Cell ◽  
Specific Antibody ◽  
Interleukin 2 ◽  
Antibody Responses ◽  
T Cell Help

scholarly journals Transient CD4+T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses

2016 ◽  
Vol 90 (9) ◽  
pp. 4278-4288 ◽  
Author(s):  
Nicholas M. Provine ◽  
Alexander Badamchi-Zadeh ◽  
Christine A. Bricault ◽  
Pablo Penaloza-MacMaster ◽  
Rafael A. Larocca ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Specific Antibody ◽  
De Novo ◽  
Current Model ◽  
Critical Role ◽  
T Cell Responses ◽  
Antibody Responses ◽  
Cell Responses ◽  
T Cell Help

ABSTRACTWe have recently demonstrated that CD4+T cell help is required at the time of adenovirus (Ad) vector immunization for the development of functional CD8+T cell responses, but the temporal requirement for CD4+T cell help for the induction of antibody responses remains unclear. Here we demonstrate that induction of antibody responses in C57BL/6 mice can occur at a time displaced from the time of Ad vector immunization by depletion of CD4+T cells. Transient depletion of CD4+T cells at the time of immunization delays the development of antigen-specific antibody responses but does not permanently impair their development or induce tolerance against the transgene. Upon CD4+T cell recovery, transgene-specific serum IgG antibody titers develop and reach a concentration equivalent to that in undepleted control animals. These delayed antibody responses exhibit no functional defects with regard to isotype, functional avidity, expansion after boosting immunization, or the capacity to neutralize a simian immunodeficiency virus (SIV) Env-expressing pseudovirus. The development of this delayed transgene-specific antibody response is temporally linked to the expansion ofde novoantigen-specific CD4+T cell responses, which develop after transient depletion of CD4+T cells. These data demonstrate that functional vaccine-elicited antibody responses can be induced even if CD4+T cell help is provided at a time markedly separated from the time of vaccination.IMPORTANCECD4+T cells have a critical role in providing positive help signals to B cells, which promote robust antibody responses. The paradigm is that helper signals must be provided immediately upon antigen exposure, and their absence results in tolerance against the antigen. Here we demonstrate that, in contrast to the current model that the absence of CD4+T cell help at priming results in long-term antibody nonresponsiveness, antibody responses can be induced by adenovirus vector immunization or alum-adjuvanted protein immunization even if CD4+T cell help is not provided until >1 month after immunization. These data demonstrate that the time when CD4+T cell help signals must be provided is more dynamic and flexible than previously appreciated. These data suggest that augmentation of CD4+T cell helper function even after the time of vaccination can enhance vaccine-elicited antibody responses and thereby potentially enhance the immunogenicity of vaccines in immunocompromised individuals.

scholarly journals CD4+ T Cell Help Is Mandatory for Naive and Memory Donor-Specific Antibody Responses: Impact of Therapeutic Immunosuppression

2018 ◽  
Vol 9 ◽  
Author(s):  
Chien-Chia Chen ◽  
Alice Koenig ◽  
Carole Saison ◽  
Suzan Dahdal ◽  
Guillaume Rigault ◽  
...  
Keyword(s):  
T Cell ◽  
Specific Antibody ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Cd4 T Cell Help ◽  
T Cell Help

Induction of antigen-specific antibody responses by nonspecific T cell-derived helper factors

1986 ◽  
Vol 5 (3) ◽  
pp. 201-209 ◽  
Author(s):  
Michael J. Grusby ◽  
Susan K. Pierce
Keyword(s):  
T Cell ◽  
Specific Antibody ◽  
Antibody Responses

scholarly journals A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help

2017 ◽  
Vol 198 (4) ◽  
pp. 1685-1695 ◽  
Author(s):  
Meena Narayanan ◽  
Raphaela Freidl ◽  
Margarete Focke-Tejkl ◽  
Ulrike Baranyi ◽  
Thomas Wekerle ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Grass Pollen ◽  
Cell Epitope ◽  
Antibody Responses ◽  
Secondary Antibody ◽  
Epitope Peptide ◽  
B Cell Epitope ◽  
Grass Pollen Allergen ◽  
T Cell Help

scholarly journals Requirement of Cytokines for Augmentation of the Antigen-Specific Antibody Responses by Ascorbate in Cultured Murine T-Cell-Depleted Splenocytes

1998 ◽  
Vol 78 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Mitsuzumi Hitoshi ◽  
Kusamiya Makoto ◽  
Kurimoto Takafumi ◽  
Yamamoto Itaru
Keyword(s):  
T Cell ◽  
Specific Antibody ◽  
Antibody Responses

scholarly journals Selective CD4+ T Cell Help for Antibody Responses to a Large Viral Pathogen: Deterministic Linkage of Specificities

Immunity ◽  
2008 ◽  
Vol 28 (6) ◽  
pp. 847-858 ◽  
Author(s):  
Alessandro Sette ◽  
Magdalini Moutaftsi ◽  
Juan Moyron-Quiroz ◽  
Megan M. McCausland ◽  
D. Huw Davies ◽  
...  
Keyword(s):  
T Cell ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Viral Pathogen ◽  
Cd4 T Cell Help ◽  
T Cell Help

scholarly journals Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses

2006 ◽  
Vol 203 (3) ◽  
pp. 599-606 ◽  
Author(s):  
Silvia B. Boscardin ◽  
Julius C.R. Hafalla ◽  
Revati F. Masilamani ◽  
Alice O. Kamphorst ◽  
Henry A. Zebroski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymphoid Organs ◽  
Antibody Responses ◽  
Carrier Protein ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Maturation Stimulus ◽  
T Cell Help

Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.

scholarly journals Different Regions of the Malaria Merozoite Surface Protein 1 of Plasmodium chabaudi Elicit Distinct T-Cell and Antibody Isotype Responses

2001 ◽  
Vol 69 (4) ◽  
pp. 2245-2251 ◽  
Author(s):  
Stuart J. Quin ◽  
Jean Langhorne
Keyword(s):  
Amino Acids ◽  
T Cell ◽  
Specific Antibody ◽  
T Cell Response ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Interleukin 4 ◽  
T Cell Epitopes ◽  
Plasmodium Chabaudi ◽  
Antibody Isotype

ABSTRACT In this study we have investigated the antibody and CD4 T-cell responses to the well-characterized malaria vaccine candidate MSP-1 during the course of a primary Plasmodium chabaudi chabaudi(AS) infection. Specific antibody responses can be detected within the first week of infection, and CD4 T cells can be detected after 3 weeks of infection. The magnitude of the CD4 T-cell response elicited during a primary infection depended upon the region of MSP-1. In general, the highest precursor frequencies were obtained when a recombinant MSP-1 fragment corresponding to amino acids 900 to 1507 was used as the antigen in vitro. By contrast, proliferative and cytokine responses against amino acids 1508 to 1766 containing the C-terminal 21-kDa region of the molecule were low. The characteristic interleukin 4 (IL-4) switch that occurs in the CD4 T-cell population after an acute blood stage P. c. chabaudi infection was only consistently observed in the response to the amino acid 900 to 1507 MSP1 fragment. A lower frequency of IL-4-producing cells was seen in response to other regions. Although the magnitudes of the immunoglobulin G antibody responses to the different regions of MSP-1 were similar, the isotype composition of each response was distinct, and there was no obvious relationship with the type of T helper cells generated. Interestingly, a relatively high antibody response to the C-terminal region of MSP-1 was observed, suggesting that T-cell epitopes outside of this region may provide the necessary cognate help for specific antibody production.

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