Helper activity for immunoglobulin synthesis of T helper type 1 (Th1) and Th2 human T cell clones: the help of Th1 clones is limited by their cytolytic capacity.

Prete, G.; Carli, Marco De; Ricci, M; Romagnani, Sergio

doi:10.1084/jem.174.4.809

Cited by 185 publications

(108 citation statements)

References 18 publications

(10 reference statements)

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“…In vitro, a decrease in B-cell help at high T-B-cell ratios is peculiar to Th1 and most Th0 clones, because of their concomitant expression of cytolytic killing of antigen-presenting autologous B cells. 20 This cytolytic activity is perforin-mediated 10,11 and usually lacks in Th2 clones. 20 Despite similar cytokine profiles, a striking difference was found in the cytolytic potential of T-cell clones derived from MALT lymphoma or chronic gastritis.…”

Section: Discussionmentioning

confidence: 99%

“…20 This cytolytic activity is perforin-mediated 10,11 and usually lacks in Th2 clones. 20 Despite similar cytokine profiles, a striking difference was found in the cytolytic potential of T-cell clones derived from MALT lymphoma or chronic gastritis. Whereas most chronic gastritis clones expressed cytotoxicity, none of the H. pylori-specific clones (and only a few other CD4 ϩ or CD8 ϩ clones) from MALT lymphoma were cytolytic.…”

Section: Discussionmentioning

confidence: 99%

“…16 B cellenriched suspensions were prepared by a double-step rosetting with neuraminidase-treated sheep red blood cells, as described. 20 Peripheral blood B cell-enriched suspensions usually consisted of 68%-87% B cells, 9%-21% monocytes, and less than 1% T cells. They are referred to as B cells in this article.…”

Section: Cytokine Profile Of H Pylori-specific Gastric T-cell Clonesmentioning

confidence: 99%

“…Because most antigen-activated Th1 and Th0 clones express perforin-mediated cytotoxicity against antigen-presenting autologous B cells, 20 the cytolytic potential of H. pylori-specific clones obtained from chronic gastritis or MALT lymphoma was assessed using antigen-pulsed 51 Cr-labeled autologous EBV-B cells as targets. At an effector-to-target ratio of 10 to 1, none of the 28 H. pylori-specific clones from MALT lymphoma was able to lyse target cells.…”

Section: Lack Of Perforin-mediated Cytotoxicity To Antigen-presentingmentioning

confidence: 99%

See 3 more Smart Citations

Impaired T-cell regulation of B-cell growth in Helicobacter pylori–related gastric low-grade MALT lymphoma

D’Elios¹,

Amedei²,

Manghetti³

et al. 1999

Gastroenterology

100

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cytokine Profile Of H Pylori-specific Gastric T-cell Clonesmentioning

confidence: 99%

Section: Lack Of Perforin-mediated Cytotoxicity To Antigen-presentingmentioning

confidence: 99%

See 2 more Smart Citations

Impaired T-cell regulation of B-cell growth in Helicobacter pylori–related gastric low-grade MALT lymphoma

D’Elios¹,

Amedei²,

Manghetti³

et al. 1999

Gastroenterology

100

View full text Add to dashboard Cite

“…Th1 cells exert fasL-dependent cytotoxicity. 60,61 As mentioned, IFN-␥ has antiangiogenic effects 26,27 and is able to mediate tumor regression even when the CD4 ϩ helper cell recognizes MHC II-peptide on adjacent antigen-presenting cells. 28 Therefore, it will be important to pay attention to the distinction between Th1 and Th2 when exploiting DCs to bring about stronger cell-mediated immunity in humans.…”

Section: Mature Dcs Polarize Cd4 ϩ T Cells Toward the Th1 Phenotypementioning

confidence: 99%

Active immunization against cancer with dendritic cells: The near future

2001

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DCs 1 are antigen-presenting cells that regulate several components of the immune system. The mature or terminal stage of DC development induces specific T-cell immunity and resistance to experimental tumors in vivo. However, DC maturation is induced by inflammatory and microbial stimuli, so it is unlikely that mature DCs normally present antigens from tumor cells in cancer patients. Accordingly, clinical studies have begun in which DCs are generated ex vivo, charged with tumor antigens, exposed to maturation stimuli and reinfused to immunize patients. This approach has the potential to control responses to cancer antigens in a specific and nontoxic manner, in both vaccination and therapeutic settings.DCs can mobilize several immune resistance mechanisms. These include CD8ϩ CTLs, CD4 ϩ helper T cells, NK and NKT cells. Each of these lymphocytes recognizes targets through a distinct mechanism and has the capacity to kill tumor cells and release valuable protective cytokines like IFN-␥. CD4 ϩ T cells also provide essential help for the expansion and maintenance of CD8 ϩ cytolytic cells, while NK and NKT cells can eliminate targets that dampen presentation on MHC class I to escape CTL recognition. The stimulation and concerted action of these classes of lymphocytes can now be studied directly in patients, using ex vivo-derived DCs.Several findings have emerged from studies of healthy volunteers who have been immunized with DCs charged with model antigens, KLH protein and influenza virus matrix peptide. Mature DCs elicit a polarized Th1 type of CD4 T-cell response, only a single injection being required. Vaccination with antigen-bearing DCs also markedly improves the functional affinity of CD8 ϩ T cells. These findings are important in the context of immunotherapy because Th1 cells are more efficient helper cells in experimental models of viral infection and tumors, while high-affinity CTLs should improve recognition of tumor-derived peptides. An important caution also has surfaced when DCs are not adequately differentiated. Immature DCs can silence adaptive T-cell responses, e.g., by inducing IL-10 -producing, T-reg cells.DC-based active immunization does not result in major shortterm toxicity in healthy subjects or cancer patients. Tumor-specific T-cell responses have been induced and detected in fresh blood specimens without the need for restimulation in vitro. However, the immune responses observed in the first protocols are still smaller than those seen naturally in acute viral infections. Occasional clinical regressions have been noted in these initial feasibility studies, particularly in melanomas, pediatric tumors, lymphomas, prostate cancers and renal cell cancers. This information, coupled with progress in DC biology, suggests many ways to improve the efficacy of this new therapy. Some relevant topics include antigen loading and DC maturation procedures, frequency and route of DC injection, efficiency of DC homing to lymphoid tissues and their longevity once there and the role of distinct DC subsets. A val...

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Human memory T cell differentiation into Th2-like effector cells is dependent on IL-4 and CD28 stimulation and inhibited by TCR ligation

1998

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Freshly isolated memory T cells primarily produced IL-2 and small amounts of IL-4 and IFN-+ after stimulation in vitro. Priming for 5 days in vitro with anti-CD28 monoclonal antibodies (mAb) alone markedly increased production of IL-4. In comparison to fresh cells, the increase in the amount of IL-4 secreted reflected a marked increase in the number of IL-4-producing cells. Stimulation with immobilized anti-CD3 mAb during priming limited subsequent IL-4 production. By contrast, IFN-+ production from in vitro primed memory T cells was directly correlated to the concentration of priming anti-CD3 mAb. IL-2 production by all restimulated cells was decreased. The differentiation of IL-4-producing cells could be blocked by antibody to IL-4 and enhanced by the addition of recombinant IL-4 as well as antibody to IFN-+ . Of note, the IL-4-producing effector cells induced from in vitro priming derived from the early CD27 pos memory T cell subset, whereas the small CD27 neg differentiated memory subset produced IL-4 without in vitro priming. The results indicate that memory T cells can be directed to differentiate into IL-4-producing effector cells by stimulation via CD28 and IL-4, whereas increasing engagement of the TCR limits Th2 memory cell differentiation.

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Helper activity for immunoglobulin synthesis of T helper type 1 (Th1) and Th2 human T cell clones: the help of Th1 clones is limited by their cytolytic capacity.

Cited by 185 publications

References 18 publications

Impaired T-cell regulation of B-cell growth in Helicobacter pylori–related gastric low-grade MALT lymphoma

Impaired T-cell regulation of B-cell growth in Helicobacter pylori–related gastric low-grade MALT lymphoma

Active immunization against cancer with dendritic cells: The near future

Human memory T cell differentiation into Th2-like effector cells is dependent on IL-4 and CD28 stimulation and inhibited by TCR ligation

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