Th2 Activities Induced During Virgin T Cell Priming in the Absence of IL-4, IL-13, and B Cells

Cunningham, Adam F.; Fallon, Padraic G.; Khan, Mahmood; Vacheron, Sonia; Acha‐Orbea, Hans; MacLennan, Ian C. M.; McKenzie, Andrew N. J.; Toellner, Kai‐Michael

doi:10.4049/jimmunol.169.6.2900

Cited by 43 publications

(85 citation statements)

References 46 publications

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“…Mice double-deficient in IL-4 and IL-13 mount an extra-follicular LN antibody response to Th2 antigens. They produce very similar numbers of IgG1-secreting plasma cells in the medullary cords as congenic wild-type mice do [18]. Nevertheless the poor IgE and to a lesser extent IgG1 levels seen in late primary and secondary antibody responses of IL-4-deficient mice indicate a positive role for IL-4 in the response in vivo [19,20].…”

Section: Introductionmentioning

confidence: 86%

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Pinpointing IL‐4‐independent acquisition and IL‐4‐influenced maintenance of Th2 activity by CD4 T cells

et al. 2004

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Naive CD4 T cells develop Th2 activity early in primary responses to alum-precipitated proteins by producing IL-4 mRNA and inducing B cells to produce + 1 and 4 switch transcripts. Both IL-4-dependent and IL-4-independent pathways for IL-4 induction are recognized, but their relative contribution to the different phases of primary Th2 responses in vivo is uncertain. We show the primary induction of IL-4 synthesis in lymph nodes responding to alumprecipitated protein is overwhelmingly in antigen-specific CD4 T cells and is unimpaired in IL-4R § -/-mice, which can produce but do not respond to IL-4 and IL-13. Ig class-switching in extra-follicular responses, reflecting Th2 activity, is also unimpaired in these mice. By contrast, 7 days after immunization -when T cells are selecting B cells in germinal centers and T cell priming has occurred -non-responsiveness to IL-4 is associated with smaller germinal centers, increased levels of T-bet and + 2a switch transcripts and reduced + 1 and 4 transcripts. These data indicate that Th2 characteristics acquired during T cell priming and the initial CD4 T cell interaction with B cells are largely IL-4-independent, whereas IL-4 production induced during priming has a significant role in maintaining the Th2 phenotype as T cells select B cells in germinal centers.

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Section: Introductionmentioning

confidence: 86%

“…These LN give a strong selective development of Th2 activity with consistent follicular and extra-follicular antibody responses [18,21,22].…”

Section: Introductionmentioning

confidence: 99%

Pinpointing IL‐4‐independent acquisition and IL‐4‐influenced maintenance of Th2 activity by CD4 T cells

et al. 2004

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“…TaqMan probes and primers were designed using Primer Express software (Applied Biosystems). Sequences for b-actin, b2-microglobulin, IL-4, g1 GT, were published previously [16,57]. Standard reaction conditions for the TaqMan RT-PCR or PCR were used on the ABI 7900.…”

Section: Real-time Semi-quantitative Rt-pcrmentioning

confidence: 99%

Early simultaneous production of intranodal CD4 Th2 effectors and recirculating rapidly responding central‐memory‐like CD4 T cells

et al. 2009

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This study characterizes the diversity of CD4 Th cells produced during a Th2 response in vivo. Kinetics of effector and memory cell differentiation by mouse OVA-specific CD4 T cells was followed during primary responses to alum-precipitated OVA. The complexity of the CD4 T response was assessed in nodes draining and distant from the site of immunization for phenotype, location and function. By 3 days IL-4-producing effector CD4 T cells developed in the draining node and a proportion of the responding cells had migrated to B-cell follicles, while yet others had left the draining node. Some of these early migrant cells were recirculating cells with a central memory phenotype. These had divided four or more times in the draining node before migrating to distant nodes not exposed to antigen. We questioned the responsiveness of these early central-memory-like cells on secondary antigen challenge at sites distant to the primary immunization. They re-entered cell cycle and migrated to B-cell follicles, much more rapidly than naïve CD4 T cells and could still be induced to produce IL-4. Their production and survival were independent of the starting frequency of antigen-specific CD4 T cells. Thus intranodal effector cells and recirculating, rapidly responding central-memory-like cells emerged simultaneously from the third day of a primary Th2 response.

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“…Semiquantitative real-time RT-PCR was done from two 25 lmthick frozen LN sections adjacent to sections used for immunohistology as described [49]. Briefly, RNA was prepared from frozen tissue sections using RNAzol B (Biogenesis, Poole, UK).…”

Section: Rt-pcrmentioning

confidence: 99%

“…Probes for cytokines and IgG1 H chain germ-line transcripts were detected via a 5 0 label with FAM (Applied Biosystems), while probes for b-actin were 5 0 -labeled with VIC (Applied Biosystems). Sequences were as described earlier [49].…”

Section: Rt-pcrmentioning

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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Th2 Activities Induced During Virgin T Cell Priming in the Absence of IL-4, IL-13, and B Cells

Cited by 43 publications

References 46 publications

Pinpointing IL‐4‐independent acquisition and IL‐4‐influenced maintenance of Th2 activity by CD4 T cells

Pinpointing IL‐4‐independent acquisition and IL‐4‐influenced maintenance of Th2 activity by CD4 T cells

Early simultaneous production of intranodal CD4 Th2 effectors and recirculating rapidly responding central‐memory‐like CD4 T cells

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

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