Mechanisms of monoclonal antibody-facilitated tolerance induction: a possible role for the CD4 (L3T4) and CD11a (LFA-1) molecules in self-non-self discrimination.
In vivo therapy with a CD4 (L3T4) monoclonal antibody is able to provide a tolerogenic milieu for a limited number of protein antigens. In this study we have analyzed the mechanisms of such tolerance to human gamma globulin, and show that tolerance is induced in adult T helper cells without a need for cellular depletion, and that it is probably not maintained by suppressor mechanisms nor by regulatory cellular circuits involving CD8+ (Ly-2+) cells. Tolerance induction is not a property peculiar to the CD4 molecule, as similar effects can be elicited with a monoclonal antibody directed to the CD11a (LFA-1) molecule. We suggest that tolerance is maintained by the functional deletion of mature T helper cells and that adhesion molecules, such as CD4, CD8 and CD11a, may play a critical role in T cell discernment of self from nonself.
Benjamin
R J
RJ
Department of Pathology, University of Cambridge, GB.
Qin
S X
SX
Wise
M P
MP
Cobbold
S P
SP
Waldmann
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000917:Antibody Formation; D000943:Antigens, Differentiation / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007116:Immunization, Passive; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors; D005719:gamma-Globulins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D016169:Lymphocyte Function-Associated Antigen-1; D005719:gamma-Globulins