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Expression and function of I region determinants on immunocompetent cells. I. Selective expression of I-C region determinants on immune cells.

We have examined the cytotoxic activity of anti-Iak serum and complement on various immune functions of BALB/c (H-2d) cells. Since the cytotoxic action of this antiserum on H-2d cells defines specificity Ia.7, an I-C region product, we have looked at the selective expression of this antigen. We have mainly used the in vitro anti-Lac2 response to study the cells involved in the induction and regulation of antibody. The data presented here show that Ia.7 is present on both IgM and IgG precursor B cells and in lesser amounts on plaque-forming cells. The antiserum also recognizes with less efficiency a product on specific T suppressor cells, which is possibly coded for by the adjacent I-J subregion. Both fluorescence and functional tests indicate the absence of Ia.7 on macrophages. It is also lacking on T helper cells. When we tested the antiserum on the in vitro cytotoxic responses to alloantigens, we found that neither T effector cells nor their precursors were affected.

Animals

Regulatory role of suppressor T cells in the expression of delayed-type hypersensitivity in mice. I. Transient appearance of suppressor T cells for the expression of delayed footpad reaction induced with lipid-conjugated lysozyme.

Delayed footpad reaction (FPR) to lysozyme (Lys) in mice was induced without antibody responses by lipid-conjugated lysozyme (D.Lys). This FPR was suppressed by priming s.c. with a high dose (10 mg) of Lys 2 weeks previously (unresponsiveness). Spleen cells from the unresponsive mice suppressed antigen-specifically FPR in mice previously immunized with D.Lys, and also suppressed passive transfer of FPR by D.Lys-immune lymphoid cells into normal mice. The suppressive activity of the spleen cells was abolished by treatment with anti-phi anti-serum and complement. The suppressor cells occurred also in the thymus of unresponsive mice. Unresponsiveness was induced in mice immediately after priming with Lys and persisted at least up to 7 weeks after the induction. In contrast, suppressor cells appeared only 2 weeks after induction of unresponsiveness in both the spleen and the thymus but were no longer detectable 3-7 weeks later, although donor mice remained fully unresponsive. These results suggest that antigen-specific suppressor T cells are involved in the regulation of the expression of FPR only for a definite period of time in unresponsive mice.

Animals

Cyclic kinetics and mathematical expression of the primary immune response to soluble antigen. VII. The conveyer hypothesis and its mathematical expression.

The conveyer hypothesis is based on the fact that because of clone predetermination, antibody production takes place in an organism without the presence of antigen as a result of natural cell differentiation. Soluble antigen is an analogue of a specific mitogen which gives rise to reproduction mainly of cells carrying on their surface the immunoglobulin receptors to the given antigen. The mathematical model of the conveyer hypothesis takes into account the initial conditions, among them the background level of antibody-producing cells before injection of a soluble antigen, migration of precursor cells in the draining lymphoid organ, and the rate of precursor differentiation, including the rate of the change of the immunoglobulin receptor number on the cell surface. Changes of antigen concentration in blood determine the intensity of precursor proliferation. Comparison of real experiments (intraperitoneal injections of capsular antigen of Pasteurella pestis into inbred mice) with calculations done on the basis of the developed mathematical model shows a definite qualitative resemblance with the kinetics of antibody-producing cells and free antibodies as well as with the decrease of free antigen concentration in blood. In spite of some differences between model experiments and real experiments the conveyer hypothesis and its mathematical model appear suitable for describing the primary immune response of mice immunized with low doses of capsular antigen of Pasteurella pestis.

Animals

A novel neoadjuvant immunotherapy confers improved overall survival in oral cancer patients with low tumor PD-L1 expression The IT-MATTERS Clinical trial - Prognostic role of tumor PD-L1 expression.

OBJECTIVE: Five-year overall survival (OS) remains&#xa0;<&#xa0;50% for patients with resectable, locally advanced (LA) primary oral squamous cell carcinoma (OSCC) and soft palate, receiving current standard of care (SOC). The aim of our study was to examine neoadjuvant Leukocyte Interleukin Injection (LI) with CIZ (intravenous low dose cyclophosphamide, indomethacin and zinc multivitamins) effect on OS, in low-risk (LR) OSCC patients. PATIENTS AND METHODS: In a randomized, controlled Phase 3 trial, treatment-na&#xef;ve locally advanced patients, with stage III/IVa OSCC and soft-palate cancer, had surgical tumor samples assessed for pre-defined thresholds of PD-L1 tumor proportion score (TPS). OS was analyzed using proportional hazard models for LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC, in the intention-to-treat (ITT) population. RESULTS: OS was superior in low risk (LR) patients receiving LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC compared to SOC; OS advantage hazard ratio (HR) 0.64, p&#xa0;=&#xa0;0.0569 (without selecting for N0, PD-L1 TPS&#xa0;<&#xa0;10%), and the Kaplan-Meier (K-M) lifetable achieved significance (log rank p&#xa0;=&#xa0;0.0340) favoring LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC. Applying the selection criteria (cN0 and TPS&#xa0;<&#xa0;10%) to ITT, OS reached HR 0.34p&#xa0;=&#xa0;0.0012, Kaplan-Meier log rank p&#xa0;=&#xa0;0.0015. The ITT LR cohort (cN0 and TPS&#xa0;<&#xa0;10%) achieved a HR 0.26 (p&#xa0;=&#xa0;0.0023), Kaplan-Meier log rank p&#xa0;=&#xa0;0.0013, supported by progression free survival (PFS) HR 0.43, p&#xa0;=&#xa0;0.0178, Kaplan-Meier log rank p&#xa0;=&#xa0;0.0431, with 32% absolute survival advantage over control at 60&#xa0;months. CONCLUSIONS: Significant OS prolongation was observed in ITT population for LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC, in LR and in ITT LR cN0, PD-L1TPS&#xa0;<&#xa0;10% cohort having locally advanced squamous cell carcinoma tumors in oral cavity/soft-palate. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01265849; EudraCT (Identifier: 2010-019952-35).

Humans

The expression of Ia antigens on immunocompetent cells in the quinea pig. I the differential expression of Ia antigens on T cell subpopulations.

We have examined the effect of negative selection with anti-Ia serum and C on a number of T cell functions and have clearly defined two subpopulations of guinea pig T lymphocytes. One subpopulation is susceptible to the lytic effects on anti-Ia serum and C and includes the majority of the primed T cells which proliferate and which produce migration inhibition factor in response to specific antigen stimulation in vitro. The lytic effects of anti-Ia serum were directed against the antigen-specific T cell and not an accessory cell such as a macrophage or nonantigen-specific T cell. No evidence for allelic exclusion of the Ia antigens of the antigen-responsive cell could be demonstrated. The susceptibility of the mitogen-responsive T cell to lysis by anti-Ia serum and C varied with the mitogen used, anatomic origin of the T cell, and the strain of animals studied. A second subpopulation of T cells is completely resistant to the lytic effects of anti-Ia serum and C and includes the primed T helper cell and the T cell that proliferates in response to alloantigenic stimulation in the MLR.

Animals