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NATURE REVIEWS | IMMUNOLOGY VOLUME 3 | MAY 2003 | 359

Schistosomes — the para-sitic worms that arethe causative agentof schistosomiasis— chronicallyinfect ~200 mil-lion individualsin 76 countries,mainly in tropicaland sub-tropicalareas. When adultSchistosoma man-soni begin to pro-duce eggs, the hostimmune response isbiased towards a T helper 2(T

H2)-cell response, with the

key cytokine driving this polarizationbeing interleukin-4 (IL-4). Recentresearch has greatly increased ourunderstanding of how microbial com-ponents can drive the development ofT

H1 responses — but so far, we have

had little understanding of the micro-bial components that drive T

H2

responses. Now, Gabriele Schramm et al., reporting in the Journal ofBiological Chemistry, have character-ized a factor in S. mansoni eggs thatcould be responsible for the switch to aT

H2 response.Previously, work in the same labo-

ratory established that the IL-4-inducing factor in S. mansoni eggswas a secreted glycoprotein. In thecurrent study, a protein, which theauthors named IPSE (IL-4-inducingprinciple from S. mansoni eggs), wasisolated and characterized. Size deter-mination gave a molecular weight of40 kDa; this decreased to ~20 kDaunder reducing conditions, so theauthors suggest that IPSE is ahomodimer. Analysis indicated thatIPSE is identical to antigen α

1, a fac-

tor that was identified previously in S. mansoni eggs but has not been fullycharacterized.

In response to exposure to S. man-soni egg antigen extract (SmEA),basophils degranulate rapidly andrelease IL-4 and other inflammatorymediators. Is IPSE alone responsible

for these effects? The results of func-tional in vitro assays in which humanbasophils were incubated with wholeSmEA, SmEA fractions and recombi-nant IPSE, and the fact that antibod-ies raised against recombinant IPSEinhibited the activation of basophilsby SmEA, indicated that IPSE is thesole factor responsible for thebasophil-activating effects of SmEA.In addition, it was already known thatthe presence of IgE is required forSmEA to have an effect on basophils.Further analysis confirmed that IPSEcan bind IgE, indicating that it is thecrosslinking of receptor-bound IgEthat accounts for IPSE-mediatedbasophil activation.

The characterization of IPSEcould prove to be an important stepforward in our understanding of theways in which microbial products canpolarize the T-cell response to T

H2

cells. Research to characterize thenature of the interaction betweenIPSE and IgE is now underway.

Sheilagh Clarkson, Associate Editor,Nature Reviews Microbiology

References and linksORIGINAL RESEARCH PAPER Schramm, G. et al. Molecular characterization of an interleukin-4-inducing factor from Schistosoma mansoni eggs. J. Biol. Chem. 6 March 2003(DOI:10.1074/jbc.M300497200)FURTHER READING Pearce, E. J. & MacDonald,A. S. The immunobiology of schistosomiasis.Nature Rev. Immunol. 2, 499–511 (2003)

‘Eggstra’ clues to helminthinfections

I M M U N E R E G U L AT I O N IN BRIEF

CD4+ T cells are required for secondary expansion andmemory in CD8+ T lymphocytes.Janssen, E. M. et al. Nature 421, 852−856 (2003)

Requirement for CD4+ T-cell help in generatingfunctional CD8+ T-cell memory.Shedlock, D. J. & Shen, H. Science 300, 337−339 (2003)

Defective CD8+ T-cell memory following acute infectionwithout CD4+ T-cell help.Sun, J. C. & Bevan, M. J. Science 300, 339−342 (2003)

Understanding how memory responses are generated is crucial ifwe are to develop improved vaccine strategies. Three recent papershave addressed the issue of whether T-cell help is required for thegeneration of functional CD8+ memory T cells. For primary CD8+

T-cell responses to certain antigens, CD4+ T cells are required to ‘license’ antigen-presenting cells (APCs) — thought to bemediated by CD40 signalling — to generate a response. Butprimary CD8+ T-cell responses to infectious agents do not oftenrequire T-cell help, because microbial products provide their ownimmunostimulatory signals for the direct activation of APCs.These studies now show that CD4+ T-cell help is necessary duringthe priming phase, but not during the recall response itself, togenerate an effective CD8+ memory T-cell response.

Essential role for caspase 8 in T-cell mediatedhomeostasis and T-cell mediated immunity.Salmena, L. et al. Genes Dev. 17, 883−895 (2003)

The role of caspase-8 in immunity is uncertain as disruption ofthe gene is lethal during embryogenesis. In this new study, micewith a T-cell-specific caspase deficiency were shown to havenormal thymic output of T cells but decreased numbers ofperipheral T cells. T-cell clonal expansion was also impaired —apparently owing to reduced survival rather than a defect in T-cellactivation — and the mice were unable to mount effective anti-viral responses.

ISKAP-55 regulates integrin adhesion and formation ofT cell–APC conjugates. Wang, H. et al. Nature Immunol. 4, 366−374 (2003)

A function for the T-cell adaptor protein SKAP55 has long beensought. An initial clue to its role came from previous observationsthat SKAP55 binds to another T-cell adaptor, ADAP, a regulator ofintegrin clustering. This study shows that similar to APAP, increasedexpression of SKAP55 in cell lines or primary mouse T cells potentlyupregulates the formation of T-cell-APC (antigen-presenting cell)conjugates in vitro. It seems that SKAP55 mediates this effect byupregulating integrin clustering and adhesion. So, SKAP55 joinsADAP as a crucial component of the still poorly understood‘inside out’ signalling pathway that regulates conjugate formation.

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