Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans
Bacterial pathogens expressing capsular polysaccharides are common causes of mucosal infections (pneumonia, intestinal), as well as often fatal, invasive infections (meningitis, bloodstream infections) in children and adults worldwide. These chemically simple but structurally complex carbohydrate st...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-02-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/7/1/18 |
| _version_ | 1798038492136079360 |
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| author | Vibha Jha Edward N. Janoff |
| author_facet | Vibha Jha Edward N. Janoff |
| author_sort | Vibha Jha |
| collection | DOAJ |
| description | Bacterial pathogens expressing capsular polysaccharides are common causes of mucosal infections (pneumonia, intestinal), as well as often fatal, invasive infections (meningitis, bloodstream infections) in children and adults worldwide. These chemically simple but structurally complex carbohydrate structures on the bacterial surface confer resistance to recognition and clearance by the immune system through a range of mechanisms. Such recognition of capsular polysaccharides may be reduced by their limited ability to directly stimulate B cells and the T cells that may facilitate these humoral responses. The capsules may promote the evasion of complement deposition and activation and may sterically shield the recognition of other subjacent protein antigens by innate factors. Antibodies to capsular polysaccharides, elicited by infection and vaccines, may overcome these obstacles and facilitate bacterial agglutination at mucosal surfaces, as well as the opsonization and clearance of these organisms in tissues and the systemic compartment. However, the immunogenicity of these antigens may be limited by their lack of direct recognition by T cells (“T-independent„ antigens) and their restricted ability to generate effective memory responses. In this review, we consider the mechanisms by which polysaccharides may initiate B cell responses and specific antibody responses and the role of T cells, particularly CD4+ follicular helper (TFH) cells to support this process. In addition, we also consider more recent counterintuitive data that capsular polysaccharides themselves may bind major histocompatibility antigen HLA class II to provide a more physiologic mechanism of T cell enhancement of B cell responses to capsular polysaccharides. Defining the contributions of T cells in the generation of effective humoral responses to the capsular polysaccharides will have important implications for understanding and translating this immunobiology for the development of more effective vaccines, to prevent the morbidity and mortality associated with these common mucosal and invasive pathogens in populations at risk. |
| first_indexed | 2024-04-11T21:40:57Z |
| format | Article |
| id | doaj.art-1a866ff178734645b13a843ba1beb966 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T21:40:57Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-1a866ff178734645b13a843ba1beb9662022-12-22T04:01:35ZengMDPI AGVaccines2076-393X2019-02-01711810.3390/vaccines7010018vaccines7010018Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in HumansVibha Jha0Edward N. Janoff1Mucosal and Vaccine Research Program Colorado (MAVRC), Infectious Diseases, University of Colorado Denver, Aurora, CO 80045, USAMucosal and Vaccine Research Program Colorado (MAVRC), Infectious Diseases, University of Colorado Denver, Aurora, CO 80045, USABacterial pathogens expressing capsular polysaccharides are common causes of mucosal infections (pneumonia, intestinal), as well as often fatal, invasive infections (meningitis, bloodstream infections) in children and adults worldwide. These chemically simple but structurally complex carbohydrate structures on the bacterial surface confer resistance to recognition and clearance by the immune system through a range of mechanisms. Such recognition of capsular polysaccharides may be reduced by their limited ability to directly stimulate B cells and the T cells that may facilitate these humoral responses. The capsules may promote the evasion of complement deposition and activation and may sterically shield the recognition of other subjacent protein antigens by innate factors. Antibodies to capsular polysaccharides, elicited by infection and vaccines, may overcome these obstacles and facilitate bacterial agglutination at mucosal surfaces, as well as the opsonization and clearance of these organisms in tissues and the systemic compartment. However, the immunogenicity of these antigens may be limited by their lack of direct recognition by T cells (“T-independent„ antigens) and their restricted ability to generate effective memory responses. In this review, we consider the mechanisms by which polysaccharides may initiate B cell responses and specific antibody responses and the role of T cells, particularly CD4+ follicular helper (TFH) cells to support this process. In addition, we also consider more recent counterintuitive data that capsular polysaccharides themselves may bind major histocompatibility antigen HLA class II to provide a more physiologic mechanism of T cell enhancement of B cell responses to capsular polysaccharides. Defining the contributions of T cells in the generation of effective humoral responses to the capsular polysaccharides will have important implications for understanding and translating this immunobiology for the development of more effective vaccines, to prevent the morbidity and mortality associated with these common mucosal and invasive pathogens in populations at risk.https://www.mdpi.com/2076-393X/7/1/18T-independent antigensimmunological responsespneumococcal capsular polysaccharidepolysaccharide conjugate vaccineantibody responsememory B cellsCD4+ T cellscarbohydrate-specific T cells |
| spellingShingle | Vibha Jha Edward N. Janoff Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans Vaccines T-independent antigens immunological responses pneumococcal capsular polysaccharide polysaccharide conjugate vaccine antibody response memory B cells CD4+ T cells carbohydrate-specific T cells |
| title | Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans |
| title_full | Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans |
| title_fullStr | Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans |
| title_full_unstemmed | Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans |
| title_short | Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans |
| title_sort | complementary role of cd4 t cells in response to pneumococcal polysaccharide vaccines in humans |
| topic | T-independent antigens immunological responses pneumococcal capsular polysaccharide polysaccharide conjugate vaccine antibody response memory B cells CD4+ T cells carbohydrate-specific T cells |
| url | https://www.mdpi.com/2076-393X/7/1/18 |
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