T Helper 1 (Th1) and Th2 Characteristics Start to Develop During T Cell Priming and Are Associated with an Immediate Ability to Induce Immunoglobulin Class Switching

Toellner, Kai‐Michael; Luther, Sanjiv A.; Sze, Daniel Man-Yuen; Choy, Richard; Taylor, D.L.; MacLennan, Ian C. M.; Acha‐Orbea, Hans

doi:10.1084/jem.187.8.1193

Cited by 206 publications

(228 citation statements)

References 67 publications

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“…In vitro, CD40 ligand (CD40L) upregulates the expression of IL-12 in cultured DCs 7, but this may not happen in vivo for the following reason: CD4-dependent recognition of foreign proteins presented by DCs evokes a primary CD4 T cell cytokine response that is almost exclusively IL-4 and is associated with the production of IgG1 (Th2)- but not IgG2a (Th1)-specific antibodies 1. If IL-12 is produced by CD40L-activated DCs during responses to protein antigens, it is not sufficient to bias the CD4 response to Th1 cytokines and IgG2a antibody production.…”

Section: Role Of Ox40 and Cd28 In Priming Cd4 Cells: Rapid Expansion mentioning

confidence: 99%

“…(A) Antigen-activated CD4 T cells are initially costimulated through CD28 by CD86 expressed on DCs 1. This CD28 signal upregulates (yellow arrow indicates intracellular signals) OX40 (red color indicates CD28 dependence).…”

Section: Figurementioning

confidence: 99%

“…These CD4 cells upregulate expression of the cytokine IL-4 and the chemokine CXCR-5, and CD4 T cells migrate to B follicles to foster GCs. (B) The situation is identical for inflammatory antigens, except that CD4 T cells are signaled by IL-12 (4; black color) in addition to CD28 1. These antigens generate CD4 cells that help both antibody and inflammatory responses, perhaps because IL-12 upregulates inflammatory chemokine receptors.…”

Section: Figurementioning

confidence: 99%

“…Recent evidence has highlighted the fact that dendritic cells (DCs) direct CD4 T cell fate during priming 1, and this has focused attention on costimulatory interactions at the initiation of CD4 immune responses. In addition to their potential to costimulate CD4 cells through CD28 ligands and IL-12, DCs have recently been shown 2 3 to express the ligand for the CD4 activation antigen, OX40.…”

mentioning

confidence: 99%

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Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells

Lane¹

2000

The Journal of Experimental Medicine

134

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Section: Role Of Ox40 and Cd28 In Priming Cd4 Cells: Rapid Expansion mentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

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Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells

Lane¹

2000

The Journal of Experimental Medicine

134

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“…After 6 months, approximately 2% of the CD4 T cells in the remote LN were Vb6 + . Antigen-dependent activation does not occur in the remote LN [12,21,24]. Nevertheless, recirculating naive Vb6 + T cells will continue to enter the draining LN.…”

mentioning

confidence: 99%

Recirculating CD4 memory T cells mount rapid secondary responses without major contributions from follicular CD4 effectors and B cells

et al. 2007

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For weeks after primary immunization with thymus-dependent antigens the responding lymph nodes contain effector CD4 T cells in T zones and germinal centers as well as recirculating memory T cells. Conversely, remote nodes, not exposed to antigen, only receive recirculating memory cells. We assessed whether lymph nodes with follicular effector CD4 T cells in addition to recirculating memory CD4 T cells mount a more rapid secondary response than nodes that only contain recirculating memory cells. Also, the extent to which T cell frequency governs accelerated CD4 T cell recall responses was tested. For this, secondary antibody responses to a superantigen, where the frequency of responding T cells is not increased at the time of challenge, were compared with those to conventional protein antigens. With both types of antigens similar accelerated responses were elicited in the node draining the site of primary immunization and in the contralateral node, not previously exposed to antigen. Thus recirculating memory cells are fully capable of mounting accelerated secondary responses, without the assistance of CD4 effector T cells, and accelerated memory responses are not solely dependent on higher T cell frequencies. Accelerated memory CD4 T cell responses were also seen in B cell-deficient mice. IntroductionPrimary immunization with thymus-dependent antigens results in specific T and B cell responses in draining lymph nodes (LN). Naive CD4 T cells enter cell cycle after being primed by cognate interaction with dendritic cells in the T zones. This results in a strong expansion of antigen-specific lymphocytes within the LN [1]. The high number of antigen-responding CD4 T cells typically is not sustained, and only a small proportion of the cells persists [2,3]. Nevertheless, CD4 memory T cells can survive for long periods without continued contact with antigen [4][5][6], although it has been reported that such antigen-deprived cells may lack competence on reactivation in vivo [7].Antigen-experienced CD4 T cells have been classified into central memory and effector memory cells [8]. Central memory T cells have a slow turnover and express high levels of CCR7 and CD62L, which are both associated with homing to T zones of lymphoid tissues. Conversely, effector memory T cells home to inflamed tissues, have a rapid turnover, and are CCR7 -CD62L low . Both effector and central memory populations in vitro respond rapidly to low doses of antigen, but while LN draining the site of immunization develop substantial populations of antigen-specific CD4 effector T cells located in the follicles and outer T zone; these are not found in the remote LN. After immunization with limiting amounts of antigen, most antigen is trapped in the LN draining the site of immunization (draining LN) and lymphocyte activation is limited to this site. Several weeks after immunization draining LN will contain effector and memory CD4 T cells. In contrast, LN remote from the site of primary immunization (remote LN) will only have received recirculating memory ...

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Defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help

et al. 1999

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Vav, a guanine nucleotide exchange factor for members of the Rho family of small GTPases, is activated through engagement of B and T lymphocyte antigen receptors. It is important for establishing the signaling threshold of the TCR, as mice lacking Vav display defective thymo-cyte selection. Here, conventional B cells are shown to develop normally in Vav-deficient mice but these mice have few B-1 B cells. The threshold for inducing B cell proliferation through BCR engagement in vitro is greater in Vav-deficient B cells. Nevertheless, in vivo the mutant mice have normal antibody responses to haptenated Ficoll. In contrast, Vav −/− mice show defective class switching to IgG and germinal center formation when immunized with haptenated protein. Interestingly, this defect is reversed in chimeras where normal T cells are present. Antigen-specific proliferation of T cells in the T zone was found to be similar in wild-type and Vav −/− mice but the induction of IL-4 mRNA and switch transcripts was specifically impaired. These results suggest that defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help.

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T Helper 1 (Th1) and Th2 Characteristics Start to Develop During T Cell Priming and Are Associated with an Immediate Ability to Induce Immunoglobulin Class Switching

Cited by 206 publications

References 67 publications

Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells

Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells

Recirculating CD4 memory T cells mount rapid secondary responses without major contributions from follicular CD4 effectors and B cells

Defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help

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