Prevalence and Activation Phenotype of Sendai Virus-Specific CD4+ T Cells

Ewing, Christine; Topham, David J.; Doherty, Peter C.

doi:10.1006/viro.1995.1329

Cited by 31 publications

(28 citation statements)

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“…Thus, our results indicate a very large expansion during the primary response, on the order of 10 3 -fold. Previously estimated frequencies of antigenspecific CD4 ϩ T cells in immunized mice have varied considerably, from values similar to those reported here to some much lower (27)(28)(29)(30)(31). Recent experiments with multimeric class I reagents have, in several cases, found extraordinarily high frequencies of antigen-specific CD8 ϩ T cells in virally infected mice, again much higher than had been predicted by other methods (9,(32)(33)(34)(35).…”

Section: Discussionsupporting

confidence: 65%

An inverse relationship between T cell receptor affinity and antigen dose during CD4⁺T cell responsesin vivoandin vitro

Rees

Bender

Teague

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

244

225

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Multimeric peptide͞class II MHC staining reagents were synthesized and shown to bind with appropriate specificity to T cell hybridomas. A small, expanded population of T cells detected with one of these reagents in peptideimmunized C57BL͞10 mice persisted for several months. This population expanded further on secondary immunization. Equating the extent of binding of this reagent to T cell receptor affinity, we saw little correlation of immunizing peptide dose to T cell receptor affinity at the peak of the primary response. However, there was an inverse relation between peptide dose and the apparent receptor affinity of the T cells that were present several months after a primary response or after a secondary stimulation either in vivo or in vitro.Tracking the cellular dynamics of antigen-specific T cell responses in vivo has been difficult, not only because the responding precursors occur at low frequency, but also because the peptide͞MHC ligand for the T cell receptor (TCR) is cell bound and of low affinity. These latter problems have been overcome by methods for producing soluble MHC molecules bearing single peptides (1-4) and for producing fluorescent multimeric versions of these molecules (5-10). The cooperative binding achieved with these multivalent ligands produces an avidity high enough that antigen-specific T cells can be detected by flow cytometry. In examining the binding of these types of reagents to T cells with receptors of known affinity for monovalent peptide͞MHC, we observed a direct correlation between the extent of multimer binding and receptor affinity (10).The phenomenon of affinity maturation is well established in B cell responses. With multiple immunizations of T celldependent antigens, B cells bearing Ig receptors of steadily increasing affinity grow to dominate the B cell pool (11, 12). These cells appear to arise by selection of somatically mutated receptors as antigen becomes limiting (13)(14)(15). Recent studies have demonstrated that T cells having higher average affinity for peptide͞MHC are selected after multiple exposures to antigen (16,17). Whether this affinity maturation is primarily the result of the experience of repeated exposure to antigen or a shaping of the T cell repertoire during antigen waning (18-20) is unknown.We examined these questions for CD4 ϩ T cells responding to a peptide presented by the mouse class II MHC molecule, IA b . We tracked the frequency and relative affinities of peptide͞MHC-binding T cells during both primary and secondary immune responses. Our results show that with repeated or prolonged exposure to antigen, limiting doses of antigen select for T cells with higher-affinity receptors.

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Section: Discussionsupporting

confidence: 65%

An inverse relationship between T cell receptor affinity and antigen dose during CD4⁺T cell responsesin vivoandin vitro

Rees

Bender

Teague

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

244

225

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“…In addition, studies examining CMV-specific CD4 T cells following both acute and latent CMV infection reported induced cell surface expression of CD49d as well as increased cell surface expression of CD11a (29). Furthermore, CD11a cell surface expression is increased on acute and memory CD4 T cells following infection with recombinant VACV, as well as following Salmonella infection (20, 25) and Sendai virus-specific memory CD4 T cells express high levels of CD49d (28, 30). These studies further substantiate our data indicating that the combined use of CD11a and CD49d cell surface expression patterns can be utilized to track antigen-specific CD4 T cells following viral infections.…”

Section: Discussionmentioning

confidence: 99%

Quantifying Antigen-Specific CD4 T Cells during a Viral Infection: CD4 T Cell Responses Are Larger Than We Think

McDermott

Varga

2011

The Journal of Immunology

131

138

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The number of virus-specific CD8 T cells increases substantially during an acute infection. Up to 90% of CD8 T cells are virus-specific following lymphocytic choriomeningitis virus (LCMV) infection. In contrast, studies identifying virus-specific CD4 T cell epitopes have indicated that CD4 T cells often recognize a broader array of antigens than CD8 T cells consequently making it difficult to accurately quantify the total magnitude of pathogen-specific CD4 T cell responses. Here we show that following LCMV infection CD4 T cells become CD11ahiCD49d+ and retain this expression pattern into memory. During the effector phase, all of the LCMV-specific IFN-γ+ CD4 T cells display a CD11ahiCD49d+ cell surface expression phenotype. In addition, only memory CD11ahiCD49d+ CD4 T cells make IFN-γ following stimulation. Furthermore, upon secondary LCMV challenge, only CD11ahiCD49d+ memory CD4 T cells from LCMV-immune mice undergo proliferative expansion, demonstrating that CD11ahiCD49d+ CD4 T cells are truly Ag-specific. Using the combination of CD11a and CD49d, we demonstrate that up to 50% of the CD4 T cells are virus-specific during the peak of the LCMV response. Our results indicate that the magnitude of the virus-specific CD4 T cell response is much greater than previously recognized.

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“…Despite the predominance of CD45RB lo CD8 + T cells in BAL from day 10 of Sendai virus infection, Sendai virus‐specific effector CTL were found in both CD45RB hi and CD45RB lo CD8 + BAL populations 35 . Similarly, Sendai virus‐specific CD4 + Th memory cells were found in both CD45RB hi and CD45RB lo spleen cell populations 36 …”

Section: Discussionmentioning

confidence: 87%

Phenotypic analysis of local cellular responses in calves infected with bovine respiratory syncytial virus

et al. 1999

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Changes in lymphocyte subsets in the trachea, pulmonary tissue, bronchoalveolar lavage (BAL), peripheral blood and bronchial lymph node (BLN) of gnotobiotic calves infected with bovine respiratory syncytial virus (BRSV) were analysed by flow cytometry. Following BRSV infection, virus titres in the nasopharynx reached a peak between days 5 and 7 and infection was resolving from day 10. Although calves did not develop signs of clinical respiratory disease, there was evidence of gross pneumonia and histological changes typical of BRSV bronchiolitis, which were most extensive from day 710 of infection. Following BRSV infection there was a recruitment of CD8+ T cells into the trachea and lung, which peaked on day 10 after infection. Thus, there were approximately equal numbers of CD8+ and CD4+ T cells in the lung and trachea of uninfected calves, whereas by day 10 of infection, CD8+ cells outnumbered CD4+ cells by 3:1 in the lungs and 6:1 in the trachea of the infected calves. Although the increase in CD4+ T cells into the lungs was less marked than that of CD8+ T cells, changes in expression of CD45R, CD45RO, L-selectin and interleukin-2 receptors all suggested that CD4+ T cells were activated during BRSV infection. Changes in gamma delta T cells were not observed in BRSV-infected calves. There was a marked increase in B cells in the BLN after infection and BLN CD4+ T cells changed from the majority expressing L-selectin and CD45R in uninfected calves to a predominance of L-selectin- CD45R- CD45RO+ phenotype, 10 days after infection. In conclusion, CD8+ T cells constitute the major lymphocyte subpopulation in the respiratory tract of calves recovering from BRSV infection.

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Prevalence and Activation Phenotype of Sendai Virus-Specific CD4+ T Cells

Cited by 31 publications

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An inverse relationship between T cell receptor affinity and antigen dose during CD4⁺T cell responsesin vivoandin vitro

An inverse relationship between T cell receptor affinity and antigen dose during CD4⁺T cell responsesin vivoandin vitro

Quantifying Antigen-Specific CD4 T Cells during a Viral Infection: CD4 T Cell Responses Are Larger Than We Think

Phenotypic analysis of local cellular responses in calves infected with bovine respiratory syncytial virus

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Prevalence and Activation Phenotype of Sendai Virus-Specific CD4+ T Cells

Cited by 31 publications

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An inverse relationship between T cell receptor affinity and antigen dose during CD4+T cell responsesin vivoandin vitro

An inverse relationship between T cell receptor affinity and antigen dose during CD4+T cell responsesin vivoandin vitro

Quantifying Antigen-Specific CD4 T Cells during a Viral Infection: CD4 T Cell Responses Are Larger Than We Think

Phenotypic analysis of local cellular responses in calves infected with bovine respiratory syncytial virus

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An inverse relationship between T cell receptor affinity and antigen dose during CD4⁺T cell responsesin vivoandin vitro

An inverse relationship between T cell receptor affinity and antigen dose during CD4⁺T cell responsesin vivoandin vitro