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
1986 ◽  
Vol 16 (9) ◽  
pp. 1037-1042 ◽  
Author(s):  
Robin E. Callard ◽  
Susan H. Smith ◽  
John G. Shields ◽  
Roland J. Levinsky

1998 ◽  
Vol 78 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Mitsuzumi Hitoshi ◽  
Kusamiya Makoto ◽  
Kurimoto Takafumi ◽  
Yamamoto Itaru

2016 ◽  
Vol 90 (9) ◽  
pp. 4278-4288 ◽  
Author(s):  
Nicholas M. Provine ◽  
Alexander Badamchi-Zadeh ◽  
Christine A. Bricault ◽  
Pablo Penaloza-MacMaster ◽  
Rafael A. Larocca ◽  
...  

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.


2001 ◽  
Vol 69 (4) ◽  
pp. 2245-2251 ◽  
Author(s):  
Stuart J. Quin ◽  
Jean Langhorne

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.


2018 ◽  
Vol 9 ◽  
Author(s):  
Chien-Chia Chen ◽  
Alice Koenig ◽  
Carole Saison ◽  
Suzan Dahdal ◽  
Guillaume Rigault ◽  
...  

1995 ◽  
Vol 63 (1) ◽  
pp. 168-174 ◽  
Author(s):  
K R Myers ◽  
P Beining ◽  
M Betts ◽  
H Snippe ◽  
J Inman ◽  
...  

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