GRAFT-INFILTRATING T-HELPER CELLS, CD45RC PHENOTYPE, AND TH1/TH2-RELATED CYTOKINES IN DONOR-SPECIFIC TRANSFUSION-INDUCED TOLERANCE IN ADULT-RATS

被引:78
作者
JOSIEN, R
PANNETIER, C
DOUILLARD, P
CANTAROVICH, D
MENORET, S
BUGEON, L
KOURILSKY, P
SOULILLOU, JP
CUTURI, MC
机构
[1] INSERM,U437,F-44035 NANTES 01,FRANCE
[2] INST PASTEUR,INSERM,U277,UNITE BIOL MOLEC GENE,F-75724 PARIS 15,FRANCE
关键词
D O I
10.1097/00007890-199511270-00013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Specific tolerance to LEW.1W (RT1(u)) heart allografts can be induced in adult LEW.1A (RT1(a)) rats by donor-specific blood transfusion (DST). We have previously shown that both rejected and tolerated grafts are heavily infiltrated by T lymphocytes, and that in both cases these T cells are capable of developing similar cytotoxic responses against donor cells in vitro; tolerance is therefore not due to the deletion of alloreactive T cells. At the same time, we found that the accumulation of IL-2 and IFN-gamma mRNA was decreased in tolerated grafts compared with rejected grafts, These results suggested that the induction of allograft tolerance in DST-treated animals could be mediated by anergy or suppression of graft-infiltrating Th1 cells, Although Th1 and Th2 clones have not yet been characterized in the rat, peripheral CD4(+) rat T cells can be divided into two populations, based on their expression of the isoform RC of the CD45 molecule, Upon activation, CD45RC(high) CD4(+) T cells produce IL-2 and IFN-gamma and are responsible for the induction of the graft-versus-host reaction, whereas CD45RC(low) CD4(+) T cells produce IL-4 in vitro and provide B cell help, In the present study, we show that heart allografts from both DST-treated and untreated rats were infiltrated by equivalent numbers of leukocytes, of which CD4(+) T cells also made up similar percentages. Among these CD4(+) T cells, we observed that in allografts from DST-treated recipients the CD45RC(high) population on day 5 was very significantly smaller (P = 0.004) than in the untreated group, while CD45RC(low) populations remained comparable. Moreover, using a new quantitative RT-PCR method, we found a dramatic reduction in the accumulation of IL-2, IFN-gamma, IL-10, IL-4, and IL-13 mRNA in hearts from DST-treated recipients compared with those of untreated recipients during the week following transplantation. These results show that in heart allografts from DST-treated recipients, despite phenotypic changes suggesting Th1 inhibition by Th2 imbalance, T helper function was inhibited as a whole, and that in vivo the phenotype CD4(+) CD45RC(low) does not always correlate with Th2-related cytokine-producing cells.
引用
收藏
页码:1131 / 1139
页数:9
相关论文
共 45 条
[1]   THE SYNERGY BETWEEN NAIVE AND MEMORY T-CELLS DURING ACTIVATION [J].
AKBAR, AN ;
SALMON, M ;
JANOSSY, G .
IMMUNOLOGY TODAY, 1991, 12 (06) :184-188
[2]  
ARMSTRONG H, 1987, J EXP MED, V169, P891
[3]   INTERCONVERSION OF CD45R SUBSETS OF CD4 T-CELLS INVIVO [J].
BELL, EB ;
SPARSHOTT, SM .
NATURE, 1990, 348 (6297) :163-166
[4]   HETEROGENEITY OF HELPER INDUCER LYMPHOCYTES-T .2. EFFECTS OF INTERLEUKIN-4-PRODUCING AND INTERLEUKIN-2-PRODUCING T-CELL CLONES ON RESTING LYMPHOCYTES-B [J].
BOOM, WH ;
LIANO, D ;
ABBAS, AK .
JOURNAL OF EXPERIMENTAL MEDICINE, 1988, 167 (04) :1350-1363
[5]  
BOUCHOT O, 1988, TRANSPLANTATION, V48, P918
[6]   ALLOGRAFT-REJECTION IN CD4+ T-CELL RECONSTITUTED ATHYMIC NUDE RATS - THE NONESSENTIAL ROLE OF HOST-DERIVED CD8+ CELLS [J].
BRADLEY, JA ;
SARAWAR, SR ;
PORTEOUS, C ;
WOOD, PJ ;
CARD, S ;
AGER, A ;
BOLTON, EM ;
BELL, EB .
TRANSPLANTATION, 1992, 53 (02) :477-482
[7]  
BRADLEY JA, 1992, TRANSPLANT REV, V6, P115
[8]  
BUGEON L, 1991, TRANSPLANTATION, V54, P219
[9]  
CHER DJ, 1987, J IMMUNOL, V138, P3688
[10]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299