Impact of HIV-1 Infection and Antigen Class on T Follicular Helper Cell Responses to Pneumococcal Polysaccharide–Protein Conjugate Vaccine-13
| Autor: | Edward M. Gardner, Lindsay K. Nicholson, Edward N. Janoff, James Scott, Vibha Jha, Jordan Jacobelli, Jeremy T Rahkola, Mandy Borgeson, Harsh Pratap |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Adolescent T Follicular Helper Cells Immunology Cell Adaptive Immunity Lymphocyte Activation Pneumococcal Infections Inducible T-Cell Co-Stimulator Protein Pneumococcal Vaccines Young Adult Immunogenicity Vaccine Antigen Conjugate vaccine medicine Humans Immunology and Allergy B cell Diphtheria toxin B-Lymphocytes Vaccines Conjugate AIDS-Related Opportunistic Infections business.industry Vaccination Middle Aged medicine.disease Antibodies Bacterial Pneumococcal infections Streptococcus pneumoniae Treatment Outcome medicine.anatomical_structure Immunization Case-Control Studies HIV-1 Female business Ex vivo |
| Zdroj: | The Journal of Immunology. 206:2402-2411 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Pneumococcal infections are common and serious complications of HIV-1 disease. Prevention has been compromised by the limited magnitude and quality of Ab responses to T cell–independent type 2 pneumococcal capsular polysaccharides (PPS). The pneumococcal polysaccharide–protein conjugate vaccine-13 (PCV-13) contains PPS conjugated to the T cell–dependent protein (diphtheria toxoid [DT] [CRM197]). We investigated the differential response to PPS and DT by human Ab-secreting B cells (ASC) after immunization with PCV-13 in newly diagnosed healthy HIV+ and control adults. The numbers of PPS-specific IgG ASC increased significantly and similarly in HIV+ and controls. However, DT-specific IgG ASC increased in controls but not HIV+ subjects. To determine the cellular basis of these disparate responses to DT and PPS, we characterized the frequency and activation of T follicular helper (Tfh) cells, the predominant T cell subset providing B cell help. Expression of inducible T cell costimulator (ICOS), which sustains Tfh function and phenotype, increased significantly among controls, when compared with the HIV+ group. Increases in ICOS+ Tfh correlated with changes in T-dependent, DT-specific IgG ASC in controls but not in HIV+. In contrast, ICOS expression did not correlate with T cell–independent type 2 PPS-specific ASC in either group. Of note, upon optimized ex vivo stimulation, CD4 T cells from HIV+ subjects differentiated into Tfh cells and formed synapses with Raji B cells at frequencies similar to that of controls. In summary, PCV-13–induced increase in ICOS expression on Tfh was associated with responses to DT, which was compromised in recently diagnosed healthy HIV+ adults and can be restored ex vivo by providing effective Tfh-differentiating signals. |
| Databáze: | OpenAIRE |
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