ATG induction therapy: long-term effects on Th1 but not on Th2 responses.
Antithymocyte globulin (ATG) induction therapy is associated with an increased long-term risk of infection- and cancer-related death. To analyze long-term effects of ATG induction on lymphocyte function, we prospectively assessed CD4 helper function, B-cell/monocyte and cytokine responses in 84 renal transplant recipients (ATG, n = 44) up to 1 year post-transplant. A PWM-driven allogeneic coculture system was used to assess helper function of CD4+ T cells and T-cell-dependent B-cell responses. SAC I was used for T-cell-independent stimulation of B-cell cultures. In vitro cytokine secretion and serum soluble CD30 (sCD30) were determined by enzyme-linked immunosorbent assay (ELISA). ATG induced a persistent decrease of peripheral blood lymphocyte counts compared with non-ATG treatment because of a predominant decrease of CD4+ T cells (4 months, 1 year; P < 0.0005) which was associated with a decreased CD28 expression (1 year, P = 0.02) and CD4 cell interleukin 2 (IL-2) response (4 months, P < 0.0005). However, Th2 responses (CD4 help, CD4 cell IL-4 and IL-10 responses, sCD30), which proved to be predictive of graft outcome, were not affected, and neither was the secretion of the lymphoma growth factors IL-6 and IL-10 by B cells and monocytes. Our data show that ATG induction therapy in immunological high-risk patients induces a profound long-term decrease in cell counts and Th1 but not Th2 responses of CD4+ T cells which may explain long-term effects on infection and post-transplant lymphoproliferative disease (PTLD) incidence because of inadequate T-cell control.
Weimer
Rolf
R
Department of Internal Medicine, University of Giessen, Giessen, Germany. rolf.weimer@innere.med.uni-giessen.de
Staak
Anne
A
Süsal
Caner
C
Streller
Sabine
S
Yildiz
Sevgi
S
Pelzl
Steffen
S
Renner
Fabrice
F
Dietrich
Hartmut
H
Daniel
Volker
V
Rainer
Lucy
L
Kamali-Ernst
Shirin
S
Ernst
Wolfgang
W
Padberg
Winfried
W
Opelz
Gerhard
G
D000328:Adult; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D066298:In Vitro Techniques; D007239:Infections / Q000209:etiology; D017730:Ki-1 Antigen / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018121:Receptors, Cytokine / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors
D000961:Antilymphocyte Serum; D015815:Cell Adhesion Molecules; D016207:Cytokines; D017730:Ki-1 Antigen; D018121:Receptors, Cytokine