I. A. Kondrat'eva

Effect of thymectomy on induction of tolerance and on T suppressor formation

During the last i0 years the nature of immunologic tolerance has been extensively discussed in the literature. It has not been shown that tolerance may be based on two fundamentally different processes: elimination or inactivation by an antigen of the corresponding clone of immunocompetent cells [6, 9, i0, 16] or increased activity of antigen-specific T or B suppressors, secondarily inhibiting effector cells or their precursors [8, 14, 15]. The concrete conditions under which a particular form of tolerance arises and the possibility of their coexistence and mutual transition are items for discussion [3].

[Thymus-dependence of genetic resistance to (CBA x M523)F1 lymphocytes].

The nature of cells responsible for the genetic resistance of lethally irradiated CBA mice to lymphocytes of (CBA x M523)F1 hybrids was studied. Preirradiation of the hosts was shown to abolish the resistance. The latter was generally recovered by syngeneic thymocytes or splenocytes while embryonic liver and bone marrow cells or splenocytes treated with anti-Thy-I serum plus complement before injection into host were ineffective. It is postulated that some cells with T cell characteristics are responsible for the phenomenon of parental resistance. These cells differ in several respects from T cells that mediate the transplantation immunity and from M cells that control other forms of the genetic resistance.

Induction of immunologic tolerance to thymus-dependent antigen (sheep's red blood cells) in the absence of T cells

The role of T cells in the induction of tolerance of B cells to sheeps red blood cells (SRBC) by means of cyclophosphamide (CP) was investigated. Tolerance was obtained in adult intact mice, in mice irradiated lethally and protected with syngeneic embryonic liver cells and thymocytes (TB mice), and in mice deprived of T cells—either thymectomized or lethally irradiated and protected with embryonic liver cells (B mice). This form of tolerance was shown to be due to specific elimination of T lymphocytes and, to some extent also, of B lymphocytes. Tolerogenic treatment of B mice, as also of TB mice, led to depression of their immunoreactivity. Spleen cells of tolerant B mice did not suppress the immune response of intact spleen cells. It is concluded that under the conditions investigated, tolerance of B cells can be formed without the participation of T lymphocytes.

Effect of spontaneous loss of tolerance on T and B lymphocyte function in mice

Functional activity of spleen and thymus cells of mice tolerant to sheeps red blood cells was studied 1 and 4 days after induction of tolerance. Tolerance was obtained with the aid of cyclophosphamide. Complete restoration of the immunocompetence of the thymus cells was found after 4 weeks. The functional activity of splenic T and B lymphocytes also was partly restored 4 weeks after induction of tolerance. Preliminary thymectomy weakened but did not prevent complete restoration of competence of splenic T cells. No T suppressors were found in the thymus and spleen of the tolerant animals.

Factors determining long-term chimerism of lymphoid tissue in cyclophosphamide treated mice

The conditions of origin of long-term chimerism were investigated in adult CBA mice receiving cyclophosphamide and F1(CBA×C57BL/6) spleen cells. Essential conditions are a high dose of cells (more than 50×106), a dose of cyclophosphamide of not less than 200 mg/kg, and short intervals (3–6 h) between their injections. The results are interpreted from the standpoint of the hypothesis that cyclophosphamide can induce reversible injuries in lymphocyte DNA; these injuries become fixed after contact between lymphocytes and antigen and they lead to death of the corresponding cell alone.

Immunological competence of T and B lymphocytes in clophosphamide-induced tolerance

Immunological competence of T and B lymphocytes of mice was studied 7 days after induction of tolerance by injection of a massive dose of sheeps red cells and cyclophosphamide. The ability of lymphocytes of the tolerant mice to influence cooperation between normal T and B lymphocytes also was investigated. This particular form of tolerance was shown to be due not to suppressor T cells, but to a true deficiency of “helper” T cells (in both the thymus and spleen) and, to some extent also, of B cells (in the spleen). The very small deficiency of B cells in the bone marrow was connected with the nonspecific action of cyclophosphamide. It is postulated that cyclophosphamide selectively eliminates cells proliferating under the influence of the antigen.

Syngeneity as a factor in cooperation between T- and B-lymphocytes

Effectiveness of cooperation between (CBA x C57BL/6)F1 thymocytes and CBA bone-marrow cells in the immune response to sheeps red cells was compared with syngeneic combinations of the same cells in culturein vivo. The selectiveness of cooperation between T- and B-lymphocytes of different origin also was investigated in incomplete (CBA x C57BL/6)F1→CBA chimeras obtained with the aid of cyclophosphamide, in which the donors were primed with sheeps red cells and the recipients were either intact or were tolerant to that antigen. F1 T-cells were shown to cooperate with CBA B-cells 10–50 times less effectively than with syngeneic B-cells. It is postulated that the similar antigenic structure of the cell membrane of T- and B-lymphocytes, acting in conjunction with their physical contact, increases the effectiveness of action of the T-mediator on the B-cell