Function of Macrophages in Antigen Recognition by Guinea Pig T Lymphocytes

Abstract

Recent studies indicate that histocompatibillty-linked immune response (It) 1 genes, are expressed on thymus-derived (T) lymphocytes. In the mouse, the genetically controlled difference in the IgG antibody response between high and low responders immunized with branched-chain amino acid polymers is lost in thymus-deprived mice (1). In guinea pigs, the initiation of functions thougtrt to be regulated by T lymphocytes (delayed cutaneous hypersensitivity, antigen-induced lymphocyte proliferation in vitro, and carrier function) requires the presence of the appropriate Ir gene (2). Thus, guinea pigs that lack the poly-L-lysine (PLL) gene (nonresponders) fail to develop either delayed hypersensitivity or other cellular immune phenomena upon immunization with 2,4-dinitrophenyl (DNP)-poly-L-lysine. Nonetheless, these animals are capable of recognizing DNP-PLL as a hapten and produce antibodies to DNP-PLL when this molecule is coupled to an immunogenic protein carrier (3). In addition, recent data indicate that the number of specific antigen-binding bone marrow-derived (B) lymphocytes does not differ between responders and nonresponders (4-6). Schlossman (7) has also recently shown that the antibody clones and the variable region gene pool for antibodies to a-DNP-deca-L-lysine, an antigen the response to which is controlled by the PLL gene, appear to be indentical in responder and nonresponder animals. Thus, the weight of experimental evidence suggests that the main functional role of the Ir gene product is in the process of antigen recognition by the T lymphocyte.However, an alternative explanation to these studies is that the Ir genes might be expressed in a cell that controls and regulates T-cell activation, i.e., the macrophage. A number of attempts have been made to resolve this issue by using cell transfer studies (8, 9). When spleen and lymph node cells were transferred from (2 X 13)F1 animals to lethally irradiated strain 13 guinea pigs that had been reconstituted with syngeneic bone marrow, a large percentage of the recipients developed the ability to respond to antigens controlled by the PLL gene; lethally irradiated strain 13 guinea 1 Abbreviations used in this paper: DNP, 2,4-dinitrophenyl; GL, a copolymer of L-glutamic acid and L-lysine; GT, a copolymer of L-glutarnic acid and L-tyrosine; It, immune response; LNL, lymph node lymphocytes; NGPS, normal guinea pig serum; PEC, peritoneal exudate cells; PELs, peritoneal exudate lymphocytes; PHA, phytohemagglutinin; PLL, poly-L-lysine; PPD, purified protein derivative of tuberculin.

Macrophage-Lymphocyte Clusters in the Immune Response to Soluble Protein Antigen in Vitro

“…As stressed above, functional studies have shown that macrophages and lymphocytes cooperate in the immune response (9,(11)(12)(13)(14)(15)(16)(17)(18) and some of the evidence indicates that the cooperation requires physical contact between the two cells. The clusters described here may provide a microenvironment necessary for macrophage-lymphocyte cooperation mediated by surface contact and/or soluble factors.…”

“…Thus, addition of macrophages pulsed with purified protein derivative of tuberculin (PPD) by brief exposure in vitro induces blast transformation in purified populations of syngeneic immune lymphocytes from guinea pig (11)(12)(13)(14), rabbit (9,15), and man (16,17). Some data suggest that this macrophage-lymphocyte cooperation requires physical interaction between the two cells (9,15,16) during which the macrophage presents molecules of surface-bound antigen to the lymphocyte (14)(15)(16)(17)(18). This investigation was supported by Statens L~egevidenskabelige Forskningsr~d, grants 512-1116 and 512-2685.…”

Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells.

“…If the C! structures were not allelically excluded, one could still explain the existence of independent sets of F~ cells which recognize antigen-pulsed macrophages from each parent by postulating a stable association between antigen receptor and CI structure on the T-lymphocyte membrane (15) and by requiring that, on any individual T lymphocyte, the allelic forms of CI structures were associated with distinct antigen receptors. Thus, (2 × 13)Fs cells which recognize OVA-pulsed 2 PECs would do so because they possessed a receptor for OVA closely associated with the strain 2 CI structure.…”

“…The histocompatibility restriction in the interaction of primed T lymphocytes with antigen-pulsed PECs or with B lymphocytes has previously been interpreted in terms of self-recogultion by cellular interaction (CI) structures borne by the interacting cell types (15,16). This hypothesis held that activation of primed T lymphocytes by antigen-pulsed PECs requires that the T lymphocyte recognize antigen by virtue of its specific antigenbinding receptor and that PEC and T lymphocyte each express CI structures, encoded within the I region of the MHC, which are capable of mutual recognition.…”

Antigen presentation in the murine T-lymphocyte proliferative response. I. Requirement for genetic identity at the major histocompatibility complex

“…Previous studies in the guinea pig (1,2) have demonstrated the requirement for genetic identity at the MHC in order for peritoneal exudate cells to present antigen effectively to primed T lymphocytes. Experiments designed to test whether similar genetic restrictions applied to antigen presentation by murine spleen cells are shown in Table I.…”