scholarly journals Persistent Simian Immunodeficiency Virus Infection Drives Differentiation, Aberrant Accumulation, and Latent Infection of Germinal Center Follicular T Helper Cells

2015 ◽  
Vol 90 (3) ◽  
pp. 1578-1587 ◽  
Author(s):  
Huanbin Xu ◽  
Xiaolei Wang ◽  
Naomi Malam ◽  
Pyone P. Aye ◽  
Xavier Alvarez ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
T Helper Cells ◽  
Latent Infection ◽  
T Helper ◽  
Humoral Immune ◽  
Tfh Cells ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Follicular T Helper Cells

ABSTRACTCD4+follicular T helper (Tfh) cells play a prominent role in humoral immune responses, but the mechanisms of their accumulation and infection in AIDS remain unclear. Here we found that germinal center (GC) Tfh cells, defined here as CXCR5+PD-1HIGHCD4+T cells, do not express the HIV coreceptor CCR5 yet serve as a latent reservoir in GCs. With disease progression, an expansion of GC Tfh cells is accompanied by increases in dysfunctional CD8+T cells. In contrast, Tfh precursor (CXCR5−CD4+T) cells in lymph nodes do express CCR5 and differentiate into GC Tfh cells following interleukin-6 (IL-6) and IL-21 stimulation, and viral DNA is detectable in fully differentiated GC Tfh cellsex vivo. This suggests that SIV-infected GC Tfh cells may be derived from Tfh precursor cell subsets that become infected in marginal zones and then migrate into GCs as fully mature GC Tfh cells that serve as persistent virus reservoirs. These findings suggest that viral persistence in lymph nodes drives compensatory differentiation, aberrant accumulation, and latent infection of GC Tfh cells, resulting in marked impairment of humoral immune responses.IMPORTANCEGeneration of antibodies that can effectively eliminate viruses requires interactions of B cells with highly specialized T cells in GCs of lymphoid tissues called follicular T helper cells. Here we show that in simian immunodeficiency virus infection, these cells are initially infected in a precursor stage that leads to alterations in their homing, accumulation, and function that may be responsible for the inability of human immunodeficiency virus-infected patients to generate effective antibody responses.

scholarly journals Noninfectious X4 but Not R5 Human Immunodeficiency Virus Type 1 Virions Inhibit Humoral Immune Responses in Human Lymphoid Tissue Ex Vivo

2004 ◽  
Vol 78 (13) ◽  
pp. 7061-7068 ◽  
Author(s):  
Wendy Fitzgerald ◽  
Andrew W. Sylwester ◽  
Jean-Charles Grivel ◽  
Jeffrey D. Lifson ◽  
Leonid B. Margolis
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Human Lymphoid Tissue ◽  
Hiv 1

ABSTRACT Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4+ T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4+ T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4+ T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.

scholarly journals Helminth Protein Vaccine Induced Follicular T Helper Cell for Enhancement of Humoral Immunity againstSchistosoma japonicum

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Jingyao Zhang ◽  
Wenjuan Gao ◽  
Qirui Guo ◽  
Bobo Huang ◽  
Bin Wang ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Humoral Immunity ◽  
Molecular Targets ◽  
T Helper Cell ◽  
Protein Vaccine ◽  
T Helper ◽  
Humoral Immune ◽  
Tfh Cells ◽  
Humoral Immune Responses

Protein vaccines combined with adjuvants have been widely used to induce immune responses, especially the humoral immune response, against molecular targets including parasites. Follicular T helper (Tfh) cells are the specialized providers of B-cell help, however, the induction of Tfh cells in protein vaccination has been rarely studied. Here, we report that theSchistosoma japonicumrecombinant protein (SjGST-32) combined with tacrolimus (FK506) augmented the induction of Tfh cells, which expressed the canonical markers CXCR5, BCL6, and IL-21, and enhanced the humoral immune responses in BALB/c mice. Furthermore, the expression of IL-21R on germinal center (GC) B cells and memory B cells increased in immunized mice, which indicated that IL-21 from the induced Tfh cells interacted with IL-21R for activation of B cells and maintenance of long-lived humoral immunity. Our results suggest that helminth protein vaccine combined with FK506 induces Tfh cell for stimulating humoral immune responses and inducing long-lived humoral immunity.

scholarly journals TGF-β3-expressing CD4+CD25−LAG3+ regulatory T cells control humoral immune responses

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Tomohisa Okamura ◽  
Shuji Sumitomo ◽  
Kaoru Morita ◽  
Yukiko Iwasaki ◽  
Mariko Inoue ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals REGULATION OF THE IMMUNE RESPONSE

1973 ◽  
Vol 137 (3) ◽  
pp. 721-739 ◽  
Author(s):  
Michael Hoffmann ◽  
John W. Kappler
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Immune Suppression ◽  
Antigen Recognition ◽  
Helper T Cells ◽  
Antibody Specificity ◽  
Humoral Immune ◽  
Functional Assays ◽  
Humoral Immune Responses

The specificity of antigen recognition by thymus-derived helper cells (T cells) and antibody was examined in mice, heterologous erythrocyte antigens from sheep (SRBC), goat (GRBC), burro (BRBC), chicken (CRBC), and toad (TRBC) being used. Antibody specificity was tested by a number of functional assays: hemagglutination, hemolysis, and immune suppression. The specificity of T cells was determined by titrating their ability to help the in vitro antitrinitrophenol (TNP) responses of mouse spleen cultures immunized with the hapten coupled to the various test erythrocytes as carrier. Anti-SRBC antibody cross-reacted with GRBC, but not with BRBC, CRBC, or TRBC. In contrast, SRBC-primed helper T cells cross-reacted with both GRBC and BRBC, but not with CRBC or TRBC, indicating a difference in the specificity of antigen recognition between the cellular and the humoral immune responses.

scholarly journals NFAT control of immune function: New Frontiers for an Abiding Trooper

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 260 ◽  
Author(s):  
Martin Vaeth ◽  
Stefan Feske
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Immune Responses ◽  
Physiological Function ◽  
Large Body ◽  
Immunological Tolerance ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Humoral Immune ◽  
Humoral Immune Responses

Nuclear factor of activated T cells (NFAT) was first described almost three decades ago as a Ca2+/calcineurin-regulated transcription factor in T cells. Since then, a large body of research uncovered the regulation and physiological function of different NFAT homologues in the immune system and many other tissues. In this review, we will discuss novel roles of NFAT in T cells, focusing mainly on its function in humoral immune responses, immunological tolerance, and the regulation of immune metabolism.

scholarly journals Peripheral Follicular T Helper Cells and Mucosal-Associated Invariant T Cells Represent Activated Phenotypes During the Febrile Phase of Acute Dengue Virus Infection

2020 ◽  
Vol 33 (9) ◽  
pp. 610-615
Author(s):  
Sathappan U. Preeyaa ◽  
Amudhan Murugesan ◽  
Surliappan Sopnajothi ◽  
Yean K. Yong ◽  
Hong Y. Tan ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Dengue Virus ◽  
T Helper Cells ◽  
T Helper ◽  
Dengue Virus Infection ◽  
Helper Cells ◽  
Invariant T Cells ◽  
Follicular T Helper Cells

scholarly journals Induction of Humoral Immune Responses following Vaccination with Envelope-Containing, Formaldehyde-Treated, Thermally Inactivated Human Immunodeficiency Virus Type 1

2005 ◽  
Vol 79 (8) ◽  
pp. 4927-4935 ◽  
Author(s):  
B. Poon ◽  
J. T. Safrit ◽  
H. McClure ◽  
C. Kitchen ◽  
J. F. Hsu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Thermal Treatment ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.

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