Persistence of Immunogenicity of Antigen After Uptake by Macrophages

Abstract

Macrophages have the important function of participating with other cells like polymorphonuclear leukocytes (PMNs) in the uptake of bacteria, virus, and miscellaneous foreign proteins. After the uptake of these materials, both macrophages (1, 2) and PMNs (3) can catabolize them in a rapid and efficient way. (There are important exceptions however; macrophages do not catabolize well Mycobacterium tuberculosis [4], pneumococcal polysaccharide [5], or synthetic polymers of D-amino acids [6] ). In addition, live macrophages, unlike PMNs, can interact with and induce syngeneic lymphoid cells to synthesize specific antibody (7-10). Cohn made an early attempt to correlate both functions, i.e. catabolic and immunogenic, comparing PMNs and macrophages after uptake of ~P-labeled Escherichia coli (11). He noted that the catabolism of most of the bacteria proceeded at similar rates in both cell types for a 2 hr period of observation, but that macrophages, in contrast to PMNs, showedno decrease in immunogenicity. Previously, other investigations had indicated that immunogenic material could be extracted from macrophages days or weeks after uptake of protein antigens (2, 12-15); the information, however, was mostly qualitative and its relevance remained uncertain.In the present study, we have attempted to correlate the uptake, catabolism, persistence, and immunogenicity of antigen in macrophages. Hemocyanin from Maia squinado (MSH) labeled with 181I was used as antigen. The macrophages were obtained from peritoneal exudates after the injection of proteose peptone and after in vivo uptake of MSH. Immunogenicity was tested by studying the immune response of syngeneic mice after transfer of live macrophages containing antigen. In X-irradiated recipients such macrophages induced synthesis of antibody only if lymphoid cells from normal donors were also transferred (10); thus, induction of antibody synthesis was dependent upon the interaction of macrophages and lymphoid cells. The experiments to be described show that the immunogenicity of live macrophages containing antigen persists for prolonged periods of time and is asso-* Fellow, Helen Hay Whitney Foundation. Present address:

Macrophage-Digested Antigen as Inducer of Delayed Hypersensitivity

“…These cells may degrade most of the antigen which they ingest, but in some cases they retain a small fraction of it for some time, and this is suitable for induction of antibodies (24)(25)(26). In fact, this retained fraction may be particularly evocative of antibodies.…”

Comparison of the ease of tolerance induction in thymus and bone marrow of three strains of mice

“…Using Maia squinado hemocyanin (MSH) as antigen, Unanue and Askonas (1968a) found that antigen associated with macrophages was more effective in priming animals for a subsequent secondary response than was free antigen. Macrophage-associated M SH produced a secondary re sponse in irradiated recipients provided that normal lymphoid cells were also administered.…”

“…I t is apparent from the above reports that studies of the radiationsensitivity of macrophages are conflicting (Mitchison, 1969a;Unanue and Askonas, 1968a;Roseman, 1969;Pribnow and Silverman, 1967).…”

The Role of MHC Gene Products in Immune Regulation and its Relevance to Alloreactivity

“…The discovery by Miller (12) and by Good (13) that lymphocytes differentiate into two separate classes of cells (T and B) with distinct functions, the identification of cellular immune phenomena mediated by T cells (14) and the demonstration that immune responses are regulated by helper (15,16,17) and suppressor (18,19) cells and by macrophages (20) emphasized the complexity of the immune system and the critical role played by T lymphocytes in the regulation of immunity.…”