scholarly journals SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence

2021 ◽  
Vol 17 (7) ◽  
pp. e1009761
Author(s):  
Sushma Boppana ◽  
Kai Qin ◽  
Jacob K. Files ◽  
Ronnie M. Russell ◽  
Regina Stoltz ◽  
...  
Keyword(s):  
T Cell ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
T Follicular Helper Cells ◽  
S Protein ◽  
Cell Responses ◽  
Helper Cells ◽  
Follicular Helper

T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5+PD1+ CD4 T cells). SARS-CoV-2-specific cTfh responses across all three protein specificities correlated with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, cTfh responses, particularly to the M protein, increased in convalescence, and robust cTfh responses with magnitudes greater than 5% were detected at the second convalescent visit, a median of 38 days post-symptom onset. CD4 T-cell responses declined but persisted at low magnitudes three months and six months after symptom onset. These data deepen our understanding of antigen-specific cTfh responses in SARS-CoV-2 infection, suggesting that in addition to S protein, M and N protein-specific cTfh may also assist in the development of neutralizing antibodies and that cTfh response formation may be delayed in SARS-CoV-2 infection.

scholarly journals SARS-CoV-2-specific peripheral T follicular helper cells correlate with neutralizing antibodies and increase during convalescence

2020 ◽  
Author(s):  
Sushma Boppana ◽  
Kai Qin ◽  
Jacob K Files ◽  
Ronnie M. Russell ◽  
Regina Stoltz ◽  
...  
Keyword(s):  
T Cell ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Cd4 T Cell ◽  
Spike Protein ◽  
Structural Proteins ◽  
T Follicular Helper Cells ◽  
Helper Cells ◽  
Follicular Helper ◽  
Over Time

AbstractT-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 21 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mount at least one CD4 T-cell response, and 48% of individuals mount detectable SARS-CoV-2-specific peripheral T follicular helper cells (pTfh, defined as CXCR5+PD1+ CD4 T cells). SARS-CoV-2-specific pTfh responses across all three protein specificities correlate with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, pTfh responses increase in frequency and magnitude in convalescence, and robust responses with magnitudes greater than 5% were detected only at the second convalescent visit, an average of 38 days post-symptom onset. These data deepen our understanding of antigen-specific pTfh responses in SARS-CoV-2 infection, suggesting that M and N protein-specific pTfh may also assist in the development of neutralizing antibodies and that pTfh response formation may be delayed in SARS-CoV-2 infection.Author SummarySince December 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. Most currently licensed vaccines are understood to protect against infection by inducing neutralizing antibodies. As such, ongoing COVID-19 vaccine trials have focused on antibody neutralization as a primary immunologic endpoint. It is well established that T follicular helper cells are essential to the development of neutralizing antibodies and that a subset of these cells, peripheral T follicular helper cells (pTfh), can be studied in the blood. However, little is known about Tfh responses mounted in SARS-CoV-2 infection. Here, we studied pTfh to three major structural proteins in individuals recovered from COVID-19. We find that SARS-CoV-2-specific pTfh frequencies correlate with neutralizing antibody responses, especially those directed against the spike protein. We also find that pTfh responses to SARS-CoV-2 increase over time. Our findings suggest that pTfh responses against proteins other than the spike protein may contribute to the development of neutralizing antibodies and suggests that formation of pTfh responses in SARS-CoV-2 infection may be delayed.

scholarly journals Transient Mobilization of Human Immunodeficiency Virus (HIV)-Specific CD4 T-Helper Cells Fails To Control Virus Rebounds during Intermittent Antiretroviral Therapy in Chronic HIV Type 1 Infection

2001 ◽  
Vol 75 (1) ◽  
pp. 234-241 ◽  
Author(s):  
Guislaine Carcelain ◽  
Roland Tubiana ◽  
Assia Samri ◽  
Vincent Calvez ◽  
Constance Delaugerre ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Virus Production ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Helper Cells ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT Immune control of human immunodeficiency virus (HIV) is not restored by highly active antiretroviral therapies (HAART) during chronic infection. We examined the capacity of repeated structured therapeutic interruptions (STI) to restore HIV-specific CD4 and CD8 T-cell responses that controlled virus production. Eleven STI (median duration, 7 days; ranges, 4 to 24 days) were performed in three chronically HIV-infected patients with CD4 counts above 400/mm3 and less than 200 HIV RNA copies/ml after 18 to 21 months of HAART; treatment resumed after 1 week or when virus became detectable. HIV-specific T-cell responses were analyzed by proliferation, gamma interferon (IFN-γ) production, and enzyme-linked immunospot assays. Seven virus rebounds were observed (median, 4,712 HIV-1 RNA copies/ml) with a median of 7 days during which CD4 and CD8 counts did not significantly change. After treatment resumed, the viral load returned below 200 copies/ml within 3 weeks. Significant CD4 T-cell proliferation and IFN-γ production against HIV p24 appeared simultaneously with or even before the virus rebounds in all patients. These CD4 responses lasted for less than 3 weeks and disappeared before therapeutic control of the virus had occurred. Increases in the numbers of HIV-specific CD8 T cells were delayed compared to changes in HIV-specific CD4 T-cell responses. No delay or increase in virus doubling time was observed after repeated STI. Iterative reexposure to HIV during short STI in chronically infected patients only transiently mobilized HIV-specific CD4 T1-helper cells, which might be rapidly altered by virus replication. Such kinetics might explain the failure at delaying subsequent virus rebounds and raises concerns about strategies based on STI to restore durable HIV-specific T-cell responses in chronic HIV infection.

scholarly journals Adjuvanted SARS-CoV-2 Spike Protein Elicits Neutralizing Antibodies and CD4 T Cell Responses after a Single Immunization in Mice

2020 ◽  
Author(s):  
Katharina Wørzner ◽  
Daniel J. Sheward ◽  
Signe Tandrup Schmidt ◽  
Leo Hanke ◽  
Julie Zimmermann ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Spike Protein ◽  
Cell Responses

scholarly journals Pre-existing Immunity to Japanese Encephalitis Virus Alters CD4 T Cell Responses to Zika Virus Inactivated Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Noemia S. Lima ◽  
Damee Moon ◽  
Samuel Darko ◽  
Rafael A. De La Barrera ◽  
Leyi Lin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Zika Virus ◽  
Cd4 T Cells ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

The epidemic spread of Zika virus (ZIKV), associated with devastating neurologic syndromes, has driven the development of multiple ZIKV vaccines candidates. An effective vaccine should induce ZIKV-specific T cell responses, which are shown to improve the establishment of humoral immunity and contribute to viral clearance. Here we investigated how previous immunization against Japanese encephalitis virus (JEV) and yellow fever virus (YFV) influences T cell responses elicited by a Zika purified-inactivated virus (ZPIV) vaccine. We demonstrate that three doses of ZPIV vaccine elicited robust CD4 T cell responses to ZIKV structural proteins, while ZIKV-specific CD4 T cells in pre-immunized individuals with JEV vaccine, but not YFV vaccine, were more durable and directed predominantly toward conserved epitopes, which elicited Th1 and Th2 cytokine production. In addition, T cell receptor repertoire analysis revealed preferential expansion of cross-reactive clonotypes between JEV and ZIKV, suggesting that pre-existing immunity against JEV may prime the establishment of stronger CD4 T cell responses to ZPIV vaccination. These CD4 T cell responses correlated with titers of ZIKV-neutralizing antibodies in the JEV pre-vaccinated group, but not in flavivirus-naïve or YFV pre-vaccinated individuals, suggesting a stronger contribution of CD4 T cells in the generation of neutralizing antibodies in the context of JEV-ZIKV cross-reactivity.

scholarly journals Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells

2011 ◽  
Vol 208 (5) ◽  
pp. 987-999 ◽  
Author(s):  
Laura M. Fahey ◽  
Elizabeth B. Wilson ◽  
Heidi Elsaesser ◽  
Chris D. Fistonich ◽  
Dorian B. McGavern ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infection ◽  
Cd4 T Cells ◽  
Viral Infections ◽  
Viral Persistence ◽  
Cd4 T Cell ◽  
T Follicular Helper Cells ◽  
Helper Cells ◽  
Follicular Helper

CD4 T cell responses are crucial to prevent and control viral infection; however, virus-specific CD4 T cell activity is considered to be rapidly lost during many persistent viral infections. This is largely caused by the fact that during viral persistence CD4 T cells do not produce the classical Th1 cytokines associated with control of acute viral infections. Considering that CD4 T cell help is critical for both CD8 T cell and B cell functions, it is unclear how CD4 T cells can lose responsiveness but continue to sustain long-term control of persistent viral replication. We now demonstrate that CD4 T cell function is not extinguished as a result of viral persistence. Instead, viral persistence and prolonged T cell receptor stimulation progressively redirects CD4 T cell development away from the Th1 response induced during an acute infection toward T follicular helper cells. Importantly, this sustained CD4 T cell functionality is critical to maintain immunity and ultimately aid in the control of persistent viral infection.

scholarly journals Targeting Antigen to Mouse Dendritic Cells via Clec9A Induces Potent CD4 T Cell Responses Biased toward a Follicular Helper Phenotype

2011 ◽  
Vol 187 (2) ◽  
pp. 842-850 ◽  
Author(s):  
Mireille H. Lahoud ◽  
Fatma Ahmet ◽  
Susie Kitsoulis ◽  
Soo San Wan ◽  
David Vremec ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Follicular Helper

scholarly journals Impairment of Cd4+ T Cell Responses during Chronic Virus Infection Prevents Neutralizing Antibody Responses against Virus Escape Mutants

2001 ◽  
Vol 193 (3) ◽  
pp. 297-306 ◽  
Author(s):  
Adrian Ciurea ◽  
Lukas Hunziker ◽  
Paul Klenerman ◽  
Hans Hengartner ◽  
Rolf M. Zinkernagel
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Surface Glycoprotein ◽  
Cd4 T Cell ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Virus Escape ◽  
Escape Mutants

We have shown previously that neutralizing antibodies (nAbs) are important contributors to the long-term immune control of lymphocytic choriomeningitis virus infection, particularly if cytotoxic T cell responses are low or absent. Nevertheless, virus escape from the nAb response due to mutations within the surface glycoprotein gene may subsequently allow the virus to persist. Here we show that most of the antibody-escape viral mutants retain their immunogenicity. We present evidence that the failure of the infected host to mount effective humoral responses against emerging neutralization-escape mutants correlates with the rapid loss of CD4+ T cell responsiveness during the establishment of viral persistence. Similar mechanisms may contribute to the persistence of some human pathogens such as hepatitis B and C viruses, and human immunodeficiency virus.

Sign in / Sign up

Export Citation Format

Share Document