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EXPERIMENTAL STUDIES RELATING TO THE PRODUCTION AND CLINICAL TESTING OF ANTI‐HUMAN LYMPHOCYTE SERUM
Author(s) -
Martin William John
Publication year - 1969
Publication title -
medical journal of australia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 131
eISSN - 1326-5377
pISSN - 0025-729X
DOI - 10.5694/j.1326-5377.1969.tb107193.x
Subject(s) - antibody opsonization , immunology , antibody , opsonin , immune system , immunosuppression , lymphocyte , in vivo , biology , population , antigen , medicine , microbiology and biotechnology , environmental health
The present state of knowledge of the site and mode of action of ALS is briefly reviewed. ALS achieves immunosuppression in mice primarily by opsonizing recirculating thymus‐derived lymphocytes. ALS‐treated mice are therefore analogous to neonatally thymectomized mice and are unable to initiate an immune response against tissue antigens. ALS may also be able to depress, to some extent, the cellular phase of a rejection crisis, by opsonizing “effector” lymphocytes during their transit from lymphoid organs towards the graft. However, it probably cannot depress the humoral phase of a rejection crisis. It is suggested that anti‐human lymphocyte sera (AHLS) should be chosen on the criteria of opsonizing ability and antibody specificity. The in‐vivo opsonization assay outlined in this paper can be used to detect sera with opsonizing activity and also to monitor the safety of absorption procedures aimed at removing unwanted antibodies. AHLS should be administered as purified IgG rather than as crude globulin. Tolerance to IgG should be induced in potential recipients of AHLS. AHLS should be administered at the time of grafting, with the aim of eliminating the population of thymus‐derived lymphocytes. Confining the use of AHLS to acute rejection crises may not demonstrate the true value of this agent. To be able to apply these principles, certain areas of future research must be undertaken. In many situations, the in‐vivo opsonization assay would be of value. These areas of important research are: (i) an investigation into the capacity of several species to produce opsonizing antilymphocyte antibodies; (ii) an improved method of fractionating whole serum to its IgG component, plus a definition of the physical stability of its opsonizing activity; (iii) the development of a specificity assay for the detection of antibodies within AHLS directed against non‐lymphoid cells, and the application of appropriate absorption procedures to remove unwanted antibodies; (iv) a method of inducing immunological tolerance to heterologous IgG in humans and maintaining this state; (v) most importantly, the development of an assay capable of quantitating the number of circulating thymus‐derived lymphocytes which can be used to regulate the dose and frequency of administration of AHLS.