Cell-mediated response in different forms of human toxoplasmosis

Poster

Sessions

I Parasitology

International

47

(Suppt.)(1998)

P-0897

P-0895 MMUNIZATION OF CA’lTLE AGAINST lFlEILERL4 PARVA INFECCION USING RRCOMBINANT VACCINIA VIRUSES EXPRESSING A 67 kDa SPOROZOITE SURFACE ANTIGEN AND BOVINE CYTOKINBS

283-389

361

MACROPHAGE-DERIVED IL-12 REGULATES THl,THZ DICHOTOMY INTHE EARLY PHASE OF INFECTION WITH BABESIA t.4ICRUl.l AND BABESIA RODHAlNl

l&&R*‘. Slukano S*, LIU Y*. Slumada T**, Gno K* ‘Laboratory of Vetennary Chmcal Pathobmlogy, Department of Vetennary Medical Science, Graduate School of Agricultwal and Life sclenus, The University of Tokyo, and **Veterinary Teaching Hospital, and Dcpanment of Verennary Surgery. College of Agnculture. Umversity of Osaka Prefecture,

Japan Ho&X, WaithakaM, Taracha E, Duchateau L, Musoke A, McKeever D Intenmthal LhwteckResearch Institute (ILRI), P. 0. Box 30709, Nairobi, Kenya

The causawe pro~~wans of murine babes~osis, Eabesia mirrori and Babrsio mrfhzb&are knownto have a differentcourseof infeftioe. Briefly, B. microri mfecuon IS chrome and “on-lethal, whereas B. rodhcini infection IS ac”te and lethal. Our prevmus study suggested that these dlffennas were associated with the activation of sdenic helter T tTU cell subsets. heloa T cell tvoe 1 (Thl) 1” B. microti - and h&xx T &II & 2 &2) in Bl r&&-infected mice. In order to assessthe factors which activate Th cell subsets I” the BALBic mice Infected wth B. microti or f?. rodwini. the expression of both IL-10 and IL-12 mRNA in splenic cells and the levels in serum were examined. The expression of IL-12 mRNA in splenic cells was detected a early as 12 hr sfter moctdabon (al) 1” 8. microri-infected mice, whereas 8. rod/win&infected mice spraen expressed IL-12 mRNA after a delay of 12 hr than the onsel of IL-10 mRNA expcession. Both in 8. micro”- and B. r&W-infected mice, the onset of expression of IL-10 mRNA was found at 12 hrs ai. The level of IL-12 significantly increased at 3 hr ai in 8. microti-mfeaed miceswum.whereasit not

different

Theileria parva (T. parw) is the causal agent of East Coast fever (ECF), a fatal disease of cattle chawcterized by pyrexia, transient lymphopathy, and panleukopenia. Previous studies have demonstrated that a 67 kDa sqoromite surface protein (p67) of the parasite is a target for bovine neutralizing responces. We have evaluated a recombinant vaccinia vims incorporating the p67 gene (Vp67) for its immunogenicity and protective eflicacy in cattle in conjunction with viruses incorporating the bovine IL-2 and IL-4 genes (VIL-2 and VIL4). Atier two inimdemul immunizations with 5 x lo* pfu of Vp67 in combination with VIL-2 or VIL-4, only animals immunized with Vp67 and VIL-4 produced significant amounts of p67-specific antibody. However, these animals were not protected against challenge with a 70% lethal dose of stabilated sporozoite. On the other hand, even though cattle inoculated with Vp67 and VII_-2 did not exhibit significant specific antibody or T cell responses to p67, these animals were partially protected against parasite challenge. No synergistic effect was observed when cattle were immunized with a cocktail of all three viruses. The resulti of this study demonstrate the potential of recombinant vaccinia viruses as a delivery system for vaccination of cattle against T. parve infection. The effects of other bovine cytokines will also be discussed.

P-0896

VACCINIA

VIRUS RECOMBINANT

ma

serum. No sinnificant chsnaes of IL-10 level were

dominant puducer of

rc%px,l\cl>

P-0898

EXPRESSING

THE PY2 GENE OF THEILu!CR.MSERGENTI IMMUNIZATION

in B.rodh&i-dened

observed to B. miocroli-and B. mdkxk-iefected mice senan. Both qtokines IL-10 and IL-12 levels in infected mice serum reflected the kintics in spremc mRNA expression. These results suggested that IL-12 is the major factor in the differentlatmnof Th cell to Thl cell 1x1the early phase of infection wth 8. microti. Smce ule macmphage IS the IL-12, its pmdticm fnnn macrophsges co-cultured with infected erylhrocytes were investigated in virro. Bah infected evhrwytes drectly enhanced naive splemc mawophages to express IL-I? mRNA and also to produce IL-12 protem. Although both ~“fectcd erythrocytes elwt macrophagcs to produce IL-12. in viva experiment demonstrated that IL-12 levels in B. &h&i-infected mice serum have no \~gmf~cant changes suggested that the dlffercnt faclors might control the ~llmul3uon of mxwphages M produce IL-12 m these two paruws mfecuon. Togcthcr. the results suggcstcd that the donunanl pnnunp of IL-I? waycd the dlWxcr,uil”o” oI’Th cdl* ~“lo helperT ccl1 Lypc I (Thl) lx helper T cdl type 2 (Th’?) I” the wrl) phase of the Infccwn wlh flmicmri or Rmdhaini.

CELL-MEDIATED

RESPONSE

IN DIFFERENT

:

FORMS OF HUMAN TOXOPlAShlS

OF MOUSE WITH THE

RECOMBINANTS

Dziubek 2, tarnowska H. G&ski A, Basiak W, lhjfur Medical

P

University, Warsaw, Poland

The study cwcemed aspects of ceil-mediated snd hunml responses in adults with different fwms of toxopbsmOais, in m with the clinical course of the disease. Significculldisnqlian d lha cellTbeilera

sergenti

and Korea.

caused

which

mainly

of T.sergenti

for the host immune

RTP(:hitose

and

recombinants and

w/p:W’

and w/p:?!1

respecrivrly

which

of their

strains. x~tl

recombmant expressed probferation

Most of

In

““cl lketla

(:ST

viruses &XI”

vaccinra

unmune

response

YWUS

tast).

of CD8+ lymphocyteswas only noted in the first moMh of tha dlaaWa. although enlargement

of

the wrvical lymph nodes WPI obmvMa

far

up to a year. The individuals in question were fownd lo have I@ antibodies against the p30 antigen of T. gomW, maMy in tha paid

of

disease up lo 7 months. The proportionof CD4+ lympbocytea wg sub

(‘hrlosr

type

normal in all patients of this group which were studied h the fW tvvo

cells

infected

with

months of the disease, and in most of those studied Mar. 3 act d 14

type of ]I:?? were

detected

patients with the ocular fwm of toxoplasmOS&Only had ti

in HK cells were

modlfietl

inflammation in the retina, and were also found to have spadfk I@.

m

whxh

“ntlbodxzs fuswn

to

d;lp~n

mediated response was not observed (T-lymptwcyte pmWmtbn

In the group of patients with lymphadenopathy.WI inuwead pmfm@XI

express

KKl:I

resultmp In Mu

according

Tsergentjm

We have constructed which

Tsegenti,

of

system

the

mcrease

immunized agill”st were

to pJ2

of

with

p:i2

in lmmumzed

the

these

molecules

produced

assay to RSSCS the effect of these recombmant

on cellular

underw1v

l’tutose

by 0 kD.

varcmw by the

1s

stage. A YPkD major

can be classified

p:Q

vvip:+ZI

glycosylatwn

wright

m Japan

The symptom

Among the populetmn

Both types of ~82 expressed

N-lmked

molecular

virus

Ike&

at plroplasm

Ikeda type of pi12 respectwely

vv/p:W‘

with

response.

proparty

dlstrlbutmg

at, tlus stage, ~32, is the major target

ditrerent. strains

“re wme

IhP ~mmunogemc

protozoa,

in infected cattle

causes anemia

by the protozoa

surface antgen

there

19 a bovine

T-cell V~CCU~~H nxce

1s

These patients had depressed CD4+ from CD8+

lymphocytes.

levels,

and

showed

fad Of

no madbtl