MIP-1α and MIP-1β differentially mediate mucosal and systemic adaptive immunity

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 807-814 ◽  
Author(s):  
James W. Lillard ◽  
Udai P. Singh ◽  
Prosper N. Boyaka ◽  
Shailesh Singh ◽  
Dennis D. Taub ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Cd8 T Cells ◽  
Host Cells ◽  
Secretory Iga ◽  
Specific Cell ◽  
Cellular Immune Responses ◽  
Cc Chemokines ◽  
Cellular Immune

AbstractMacrophage inflammatory protein-1α (MIP-1α) and MIP-1β are distinct but highly homologous CC chemokines produced by a variety of host cells in response to various external stimuli and share affinity for CCR5. To better elucidate the role of these CC chemokines in adaptive immunity, we have characterized the affects of MIP-1α and MIP-1β on cellular and humoral immune responses. MIP-1α stimulated strong antigen (Ag)–specific serum immunoglobulin G (IgG) and IgM responses, while MIP-1β promoted lower IgG and IgM but higher serum IgA and IgE antibody (Ab) responses. MIP-1α elevated Ag-specific IgG1 and IgG2b followed by IgG2a and IgG3 subclass responses, while MIP-1β only stimulated IgG1 and IgG2b subclasses. Correspondingly, MIP-1β produced higher titers of Ag-specific mucosal secretory IgA Ab levels when compared with MIP-1α. Splenic T cells from MIP-1α– or MIP-1β–treated mice displayed higher Ag-specific Th1 (interferon-γ [IFN-γ]) as well as selective Th2 (interleukin-5 [IL-5] and IL-6) cytokine responses than did T cells from control groups. Interestingly, mucosally derived T cells from MIP-1β–treated mice displayed higher levels of IL-4 and IL-6 compared with MIP-1α–treated mice. However, MIP-1α effectively enhanced Ag-specific cell-mediated immune responses. In correlation with their selective effects on humoral and cellular immune responses, these chemokines also differentially attract CD4+ versus CD8+ T cells and modulate CD40, CD80, and CD86 expressed by B220+ cells as well as CD28, 4-1BB, and gp39 expression by CD4+ and CD8+ T cells in a dose-dependent fashion. Taken together, these studies suggest that these CC chemokines differentially enhance mucosal and serum humoral as well as cellular immune responses.

scholarly journals Hepatic cellular immune responses in mice with “cure” and “non-cure” phenotype toLeishmania infantuminfection: importance of CD8+T cells and TGF-β production

2004 ◽  
Vol 41 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Sandra Gomes-Pereira ◽  
Olivia Roos Rodrigues ◽  
Nuno Rolão ◽  
Paulo David Almeida ◽  
Gabriela Maria Santos-Gomes
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals A highly specific assay for the detection of SARS-CoV-2-reactive CD4+ and CD8+ T cells in COVID-19 patients

2020 ◽  
Author(s):  
Henning Zelba ◽  
David Worbs ◽  
Johannes Harter ◽  
Natalia Pieper ◽  
Christina Kyzirakos-Feger ◽  
...  
Keyword(s):  
T Cells ◽  
Membrane Protein ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Functional Markers ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Gaining detailed insights into the role of host immune responses in viral clearance is critical for understanding COVID-19 pathogenesis and future treatment strategies. While studies analyzing humoral immune responses against SARS-CoV-2 were available rather early during the pandemic, cellular immunity came into focus of investigations just recently. For the present work, we have adapted a protocol, designed for the detection of rare neoantigen-specific Memory T cells in cancer patients for studying cellular immune responses against SARS-CoV-2. Both, CD4+ and CD8+ T cells were detected after 6 days of in vitro expansion using overlapping peptide libraries representing the whole viral protein. The assay readout was an Intracellular cytokine staining and flow cytometric analysis detecting four functional markers simultaneously (CD154, TNF, IL-2, IFN-γ). We were able to detect SARS-CoV-2-specific T cells in 9 of 9 COVID-19 patients with mild symptoms. All patients had reactive T cells against at least one of 12 analyzed viral antigens and all patients had Spike-specific T cells. While some antigens were detected by CD4+ and CD8+ T cells, Membrane protein was mainly recognized by CD4+ T cells. Strikingly, we were not able to detect SARS-CoV-2-specific T cells in 9 unexposed healthy individuals. We are presenting a highly specific protocol for the detection of SARS-CoV-2-reactive T cells. Our data confirmed the important role of cellular immune responses in understanding SARS-CoV-2 clearance. We showed that Spike is the most immunogenic antigen. We have introduced Membrane protein as interesting target for studying humoral immune responses in convalescent COVID-19 patients.

scholarly journals Maternal and Foetal Cellular Immune Responses in Dams Infected With High- and Low- Virulence Isolates of Neospora caninum at Mid-Gestation

2021 ◽  
Vol 11 ◽  
Author(s):  
Marta García-Sánchez ◽  
Laura Jiménez-Pelayo ◽  
Patricia Vázquez ◽  
Pilar Horcajo ◽  
Javier Regidor-Cerrillo ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Neospora Caninum ◽  
Response Dynamics ◽  
Peripheral Blood Mononuclear ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune

Bovine neosporosis is currently considered one of the main causes of abortion in cattle worldwide and the outcome of the infection is, in part, determined by Neospora caninum isolate virulence. However, the dam and foetal immune responses associated with this factor are largely unknown. We used a model of bovine infection at day 110 of gestation to study the early infection dynamics (10- and 20-days post-infection, dpi) after experimental challenge with high- and low-virulence isolates of N. caninum (Nc-Spain7 and Nc-Spain1H, respectively). In the present work, dam peripheral cellular immune responses were monitored twice a week from -1 to 20 dpi. At different time points, IFN-γ and IL-4 production was investigated in stimulated dam blood and the percentage of monocytes, NK cells, B cells and T cells (CD4+, CD8+ and γδ) in peripheral blood mononuclear cells (PBMC) were determined by flow cytometry. In addition, maternal iliofemoral lymph nodes and foetal spleen and thymus were collected at 10 and 20 dpi for the study of the same cell subpopulations. Peripheral immune response dynamics were similar after the infection with both isolates, with a significant increase in the percentage of CD4+ T cells at 6 and 9 dpi in PBMC, coincident with the higher levels of IFN-γ and IL-4 release. However, the levels of IFN-γ were significantly higher and an increase in CD8+ T cells at 9, 13 and 20 dpi was observed in the dams infected with Nc-Spain7. Nc-Spain1H infection induced higher IL4 levels in stimulated blood and a higher CD4+/CD8+ ratio in PBMC. The analysis of the maternal iliofemoral lymph node showed a significant enhancement in the percentage of NK, CD4+ and CD8+ T cells for the animals infected with the highly virulent isolate and euthanized at 20 dpi. Regarding the foetal responses, the most remarkable result was an increase in the percentage of monocytes at 20 dpi in the spleen of foetuses from both infected groups, which suggests that foetuses were able to respond to N. caninum infection at mid gestation. This work provides insights into how isolate virulence affects the maternal and foetal immune responses generated against N. caninum, which may influence the course of infection.

scholarly journals Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 126
Author(s):  
Lilin Lai ◽  
Nadine Rouphael ◽  
Yongxian Xu ◽  
Amy C. Sherman ◽  
Srilatha Edupuganti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Influenza A ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
Post Vaccination ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.

scholarly journals Cellular immune responses against HCV: T cells take a diversion in the liver

Hepatology ◽  
2004 ◽  
Vol 40 (6) ◽  
pp. 1459-1461
Author(s):  
Paul Klenerman ◽  
Nasser Semmo ◽  
Scott Ward
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Human Ebola virus infection results in substantial immune activation

2015 ◽  
Vol 112 (15) ◽  
pp. 4719-4724 ◽  
Author(s):  
Anita K. McElroy ◽  
Rama S. Akondy ◽  
Carl W. Davis ◽  
Ali H. Ellebedy ◽  
Aneesh K. Mehta ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Immune Activation ◽  
Ebola Virus ◽  
Natural Infection ◽  
University Hospital ◽  
Cellular Immune ◽  
Ebola Virus Infection

Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

scholarly journals Induction of Broad-Based Immunity and Protective Efficacy by Self-amplifying mRNA Vaccines Encoding Influenza Virus Hemagglutinin

2015 ◽  
Vol 90 (1) ◽  
pp. 332-344 ◽  
Author(s):  
Michela Brazzoli ◽  
Diletta Magini ◽  
Alessandra Bonci ◽  
Scilla Buccato ◽  
Cinzia Giovani ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Upper Respiratory Tract ◽  
Vaccine Platform ◽  
Major Health Problem ◽  
Cellular Immune Responses ◽  
Influenza Virus Hemagglutinin ◽  
Cellular Immune ◽  
The Impact

ABSTRACTSeasonal influenza is a vaccine-preventable disease that remains a major health problem worldwide, especially in immunocompromised populations. The impact of influenza disease is even greater when strains drift, and influenza pandemics can result when animal-derived influenza virus strains combine with seasonal strains. In this study, we used the SAM technology and characterized the immunogenicity and efficacy of a self-amplifying mRNA expressing influenza virus hemagglutinin (HA) antigen [SAM(HA)] formulated with a novel oil-in-water cationic nanoemulsion. We demonstrated that SAM(HA) was immunogenic in ferrets and facilitated containment of viral replication in the upper respiratory tract of influenza virus-infected animals. In mice, SAM(HA) induced potent functional neutralizing antibody and cellular immune responses, characterized by HA-specific CD4 T helper 1 and CD8 cytotoxic T cells. Furthermore, mice immunized with SAM(HA) derived from the influenza A virus A/California/7/2009 (H1N1) strain (Cal) were protected from a lethal challenge with the heterologous mouse-adapted A/PR/8/1934 (H1N1) virus strain (PR8). Sera derived from SAM(H1-Cal)-immunized animals were not cross-reactive with the PR8 virus, whereas cross-reactivity was observed for HA-specific CD4 and CD8 T cells. Finally, depletion of T cells demonstrated that T-cell responses were essential in mediating heterologous protection. If the SAM vaccine platform proves safe, well tolerated, and effective in humans, the fully synthetic SAM vaccine technology could provide a rapid response platform to control pandemic influenza.IMPORTANCEIn this study, we describe protective immune responses in mice and ferrets after vaccination with a novel HA-based influenza vaccine. This novel type of vaccine elicits both humoral and cellular immune responses. Although vaccine-specific antibodies are the key players in mediating protection from homologous influenza virus infections, vaccine-specific T cells contribute to the control of heterologous infections. The rapid production capacity and the synthetic origin of the vaccine antigen make the SAM platform particularly exploitable in case of influenza pandemic.

scholarly journals Molecular and Immunological Significance of Chimpanzee Major Histocompatibility Complex Haplotypes for Hepatitis C Virus Immune Response and Vaccination Studies

2002 ◽  
Vol 76 (12) ◽  
pp. 6093-6103 ◽  
Author(s):  
Eishiro Mizukoshi ◽  
Michelina Nascimbeni ◽  
Joshua B. Blaustein ◽  
Kathleen Mihalik ◽  
Charles M. Rice ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Hepatitis C ◽  
Immune Responses ◽  
Cellular Immune Responses ◽  
Functional Homology ◽  
Histocompatibility Complex ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several candidate vaccines and immunotherapies for these infections aim at the induction or enhancement of cellular immune responses against viral epitopes presented by common human major histocompatibility complex (MHC) alleles. To identify and characterize chimpanzee MHC class I molecules that are functionally related to human alleles, we sequenced 18 different Pan troglodytes (Patr) alleles of 14 chimpanzees, 2 of them previously unknown and 3 with only partially reported sequences. Comparative analysis of Patr binding pockets and binding assays with biotinylated peptides demonstrated a molecular homology between the binding grooves of individual Patr alleles and the common human alleles HLA-A1, -A2, -A3, and -B7. Using cytotoxic T cells isolated from the blood of hepatitis C virus (HCV)-infected chimpanzees, we then mapped the Patr restriction of these HCV peptides and demonstrated functional homology between the Patr-HLA orthologues in cytotoxicity and gamma interferon (IFN-γ) release assays. Based on these results, 21 HCV epitopes were selected to characterize the chimpanzees' cellular immune response to HCV. In each case, IFN-γ-producing T cells were detectable in the blood after but not prior to HCV infection and were specifically targeted against those HCV peptides predicted by Patr-HLA homology. This study demonstrates a close functional homology between individual Patr and HLA alleles and shows that HCV infection generates HCV peptides that are recognized by both chimpanzees and humans with Patr and HLA orthologues. These results are relevant for the design and evaluation of vaccines in chimpanzees that can now be selected according to the most frequent human MHC haplotypes.

Sign in / Sign up

Export Citation Format

Share Document