Prevention of lethal graft-versus-host disease in mice by monoclonal antibodies directed to T cells or their subsets. II. Differential effectiveness of IgG2a and IgG2b isotypes of anti-CD3 and anti-CD4 moAb.
The effects of rat anti-CD3 and anti-CD4 moAb, of the IgG2a as well as of the IgG2b subclass, on the development of lethal graft-versus-host disease (GVHD) in a fully allogeneic mouse strain combination were compared in vivo. After treatment with these moAb, mice recovered from an initial loss of body weight. Moreover, their survival significantly improved. A single dose of 200 micrograms moAb resulted in a complete and long-term survival, which was not the case after treatment with anti-CD4 IgG2a moAb. A dose of at least 1 mg anti-CD4 IgG2a was necessary to induce a tolerant state. Mice effectively treated were fully repopulated with donor-type cells. Flow cytometric analysis of the recipient spleen cells demonstrated that the moAb caused depletion, modulation or coating of T cells or a combination of these. The moAb with the highest depleting capacity appeared to be anti-CD4 IgG2b moAb. Anti-CD3 IgG2a as well as IgG2b treatment resulted in a strong modulation of CD3 surface proteins, which was found on all days examined. Modulation of CD4 surface antigens did not occur in the case of anti-CD4 IgG2a moAb treatment. Anti-CD4 IgG2b moAb treatment, on the other hand, not only caused some CD4 modulation, but also, quite unexpectedly, a significant modulation of the CD3 molecule. Coating was only observed after treatment with anti-CD4 IgG2a moAb and lasted at least 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)
Knulst
A C
AC
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Noort
W A
WA
Tibbe
G J
GJ
Benner
R
R
Savelkoul
H F
HF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001835:Body Weight; D017252:CD3 Complex / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D002678:Chimera; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007132:Immunoglobulin Isotypes / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes