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In different murine systems, delayed-type hypersensitivity (DTH) swelling responses at 24–48 hr after antigen challenge were preceeded by an early 2-hr swelling response. The 24-hr DTH response is thought to depend on this early (DTH-initiating) hypersensitivity response. In this paper we show that in the syngeneic DBA/2-SL2 routine turnout system only an early 2-hr swelling response can be evoked. This early hypersensitivity response was tumour specific and serotonin dependent. The early hypersensitivity response in contact hypersensitivity has been ascribed to antigen-specific T-cell factors. To test whether similar T-cell factors were involved in the early hypersensitivity response in this syngencic turnout system, we have transferred lymph node, spleen lymphocytes and scram from immunized mice into naive recipients. The serum was fractionated in two fractions, a 50,000–80,000 MW fraction, and a 120,000–190,000 MW fraction. In recipients of lymphocytes, total serum and the 50,000–80,000 MW fraction of the serum, an early hypersensitivity response can be evoked. So, these data suggest the involvement of specific T-cell factors in the development of an early hypersensitivity response against syngeneic tumour cells. Despite the development of an early (DTH initiating) hypersensitivity swelling response these immunized animals cannot develop a classical 24-hr swelling response. This absence of the 24-hr response in the presence of the 2-hr response is discussed in relation to the frequently observed immune suppression in tumour-bearing mice. [ABSTRACT FROM AUTHOR]

Antigen-specific T-helper factor (ThE) bears I-A determinants and is I-A restricted in its action. This I-A restriction may be explained by ThF binding, and hence approximating antigen to its own I-A determinants, thereby facilitating recognition by the T cell (I-A presentation theory), or by a recognition site for I-A on the ThF which approximates the antigen to I-A+ antigen-presenting cells (I-A recognition theory). When ThF is produced in F1 mice there may be a dissociation between the I-A phenotype of the ThF and the I-A restriction of any recognition site for I-A. In practice, ThF is made by spleen cells from (CBA × B10)F1 [(H-2k × H-2d)F1] mice pretreated with cyclophosphamide (100 mg/kg) and immunized with picrylated parental spleen cells intravenously (3 × 107). This procedure produces haplotype-restricted contact sensitivity (corresponding to the parental cells) but the unfractionated F1 ThF does not show haplotype-specific restriction in its action. In fact, the F1 mice produces two species of ThE, each bearing determinants of the I-A molecule of one parental haplotype (k or d). When the two species were separated with monoclonal anti-I-Ak and anti-I-Ad antibodies, the genetic restriction in their action corresponded to the phenotype of the I-A determinants that they carried. In a further experiment, F1 ThE was split into its constituent antigen-binding (Ag+ )and antigen non-binding (Ag-)chains by reduction, and the two species of Ag- chains separated with monoclonal anti-I-A antibodies. After complementation with the Ag+ chain, the two species of Ag- chains showed genetic restriction in their action that corresponded to the phenotype of the I-A determinants that they carried. These findings support the I-A presentation hypothesis that antigen-specific ThE acts by approximating antigen to its own I-A determinants, and hence facilitates recognition by I-A-restricted I cells. [ABSTRACT FROM AUTHOR]

Properties of macrophages isolated from Peyer's patches were compared with properties of peritoneal macrophages. We found a very low expression of all types of Fc receptors as well as a low expression of Ia antigens on Peyer's patch macrophages. No substantial changes in the levels of FcR and [a antigen expression were found during the process of ageing. The investigation of phagocytic activity showed the activated state of Peyer's patch macrophages. Comparing the surface markers of lymphocytes obtained from Peyer's patches of mice of different ages, we found no differences in the numbers of sIg+, Thy-+ or L3T4+ lymphocytes. The numbers of FcR+ and Lyt 2.2+ lymphocytes decreased markedly with age. [ABSTRACT FROM AUTHOR]

PPD-reactive T cell clones have been used to analyse the nature of T lymphocytes that are involved in the 'heterogenization' of turnout cells. This is a phenomenon where coupling turnout cells to a strong antigen (in this case PPD) causes an enhanced immune response to tumour-specific antigens to be elicited providing that the host shows T cell immunity to the strong antigen (in this case is BCG positive). Clones of T cells with the Lyt1+ 2- phenotype which were unable to mediate delayed-type hypersensitivity but which provided efficient help to hapten-primed B cells were found to potentiate anti-turnout immunity in BCG-negative syngeneic mice when immunized with Con-A-PPD coupled, X-irradiated MC6A tumour cells. There therefore appears to be a mechanism whereby a helper T cell response to one antigen can provide help for the generation of a T cell response to a linked antigen which is analogous to the well-known phenomenon of help to hapten primed B cells. Furthermore the clones of T cells that help B cells the best are those that give maximal augmentation of T cell immunity. [ABSTRACT FROM AUTHOR]

The ontogeny of the capacity of the B-lymphocyte population to produce a response which is heterogeneous with respect to antibody affinity was studied in a cell transfer system. Lethally irradiated mice were reconstituted with B cells from donors of various ages, together with adult thymus cells when the response to T-dependent antigens was studied. The animals were immunized with one of a variety of antigens one day after cell transfer and the distribution of their splenic plaque-forming cells (PFC) with respect to affinity was assayed, by hapten inhibition of plaque formation, 2 to 3 weeks after immunization. Mice reconstituted with B cells from neonatal donors produced a response of low affinity and restricted heterogeneity. With four different thymic-dependent antigens (DNP-BGG, F-BGG, DNP-KLH and Dan-KLH) the splenic B-cell population acquired the capacity to reconstitute irradiated mice to produce a normal adult-like, highly heterogeneous, high affinity PFC response between 7 and 10 days after birth. The capacity to produce a heterogeneous response to the thymic-dependent protein antigen BGG matured just slightly later, between 10 and 14 days of age. The bone marrow matures with regard to the capacity to reconstitute irradiated mice to give a heterogeneous response several days after the spleen, possibly as a consequence of the redistribution of peripheral B cells to the bone marrow. In contrast, maturation of the capacity of the splenic B-cell population to reconstitute irradiated recipients to give a heterogeneous, adult-like PFC response to three 'thymic-independent' antigens (TNP-PA, DNP-Ficoll and TNP-BA) takes place considerably later (between 3 and 4 weeks of age). These results suggest that the population of B-cell precursors which responds to thymic-dependent antigens may represent a different subpopulation of B cells from the population that responds to thymic independent antigens. Furthermore, the results suggest that these B-cell subsets mature at different times, presumably under independent controls. [ABSTRACT FROM AUTHOR]

Male and female spleen cells were compared before and after culture for their cytotoxicity to autologous-embryo fibroblasts. Cultures of male cells developed significantly greater reactivity than cultures of female cells. Moreover, while the cytotoxicity derived from cultures of male cells was totally abolished by treatment of effector cells with a mouse anti-T cells antiserum, such an antiserum had less affect on the effector cells of female mouse cultures. [ABSTRACT FROM AUTHOR]

We have studied proliferative responses to mycobacterial antigen preparation (PPD) and to non- specific stimuli of interstitial cells from the lungs of Mycobacterium tuberculosis-infected CRA mice. PPD-reactive lymphocytes appeared in the lung wall tissue in the course of chronic infection, but their proliferative capacity was totally inhibited by the lung macrophages. The latter were also able to suppress the proliferation of immune lymph node T cells. The mechanism of suppression clearly had two components, one being infection-specific and the other non-specific. Non-specific suppression was mediated mainly by prostaglandin E(PGE), whereas the specific mechanism showed only a weak influence of PGE and depended on the presence of I-J+ Lyt-2- nylon-wool-adherent cells in the responder population. Interstitial lung T or B lymphocytes were not involved in specific suppression. [ABSTRACT FROM AUTHOR]