Functional Maturation of Thymic Lymphocyte Populations in Vitro

Self Cite

105

The effects of nonspecific phytomitogens on primary plaque-forming cell (PFC) responses of mouse spleen cells to heterologous erythrocytes in vitro were studied. Spleen cell cultures treated with concanavalin A or phytohemagglutinin in vitro or established with spleen cells derived from mice injected with concanavalin A 24 h previously were similarly affected. In both cases, submitogenic doses resulted in substantial enhancement of PFC responses, whereas 10-fold larger doses were profoundly inhibitory. In contrast to the suppressive effects of mitogenic doses of phytomitogens added at culture initiation, addition of these same doses to cultures 48 h later resulted in increased PFC responses. This enhancement could be observed within 1 h after treatment and consequently could not be ascribed only to mitotic expansion of the antibody-synthesizing clone. Activation of spleen cells with specific antigen before mitogen treatment was not required for expression of the enhancing or suppressing effects on PFC responses. IgM and IgG PFC responses were similarly affected. Studies of cell interactions revealed that as few as 105 spleen cells obtained from mice treated with concanavalin A in vivo synergistically enhanced the PFC responses of 107 normal spleen cells. This enhancement was mediated by mitogen-activated T lymphocytes which were resistant to 2000 R irradiation 24 h after activation. The relevance of these observations to emerging concepts of helper and suppressor T cell activity is discussed.

Section: Treatment Of Spleen Cells With Anti-o Serum and Complement-mentioning

confidence: 85%

Section: Milogens--twice Recrystallized Concanavalin a (Con A) (Nutrmentioning

confidence: 99%

Section: Milogens--twice Recrystallized Concanavalin a (Con A) (Nutrmentioning

confidence: 99%

See 1 more Smart Citation

Biological Expressions of Lymphocyte Activation

Rich

Pierce

1973

Self Cite

105

“…In an attempt to evaluate these possibilities, an excess of adult T cells was added to 2-wk old spleen cells. 1 million lymph node cells or steroid-resistant thymocytes previously had been shown (16) to fully reconstitute the SRBC response of 10 million anti-0-treated adult spleen cells . Accordingly, 1 million adult peripheral lymph node cells or steroid-resistant thymocytes were added to 10 million neonatal spleen cells, with the results shown in Table 11 .…”

Section: Resultsmentioning

confidence: 99%

Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes.

Mosier¹,

Johnson²

1975

195

The relative functional maturity of neonatal mouse spleen T- and B-cell populations was assessed by comparing the ability to respond to the thymic-independent antigen, DNP-Ficoll, or thymic-dependent SRBC by producing antibody in vitro. Although mouse spleen cells responded to DNP-Ficoll at an earlier age than they responded to SRBC or TNP-SRBC, the reason for the lag in the T-dependent response was confounded by the finding of high numbers of suppressor T lymphocytes in the neonatal spleen. Thus, small numbers of neonatal spleen T cells or thymocytes significantly decreased the in vitro antibody response of adult spleen cells. Although B lymphocytes appear to be functionally mature soon after birth, their acitivity may be modulated by an excess of suppressor T cells; e.g., the reconstitution of helper cell function in the neonatal spleen required anti-theta treatment before addition of adult helper cells. Suppressive activity attributable to T cells seems to play a dominant role in determining the ability of the neonatal animal to react positively or negatively to antigenic stimulation.

“…Complement.--Normal or Con A-activated spleen cells were treated with AKR anti-0 C3H serum and guinea pig serum as a complement source to specifically kill T cells; as a control, spleen cells were treated with brain-absorbed anti-0 serum as described in detail previously (13). Mter treatment, graded numbers of cells were added to the MLC in 0.1-ml vol.…”

Section: Treatment Of Spleen Cells With Anti-o Serum Andmentioning

confidence: 99%

Cell-Mediated Immune Responses in Vitro

Peavy

Pierce

1974

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114

The effects of soluble concanavalin A (Con A) or Con A-activated spleen cells on the generation of cytotoxic lymphocytes (CL) in mixed leukocyte cultures (MLC) were examined. Mitogenic concentrations of soluble Con A or small numbers of Con A-activated spleen cells substantially inhibited CL responses. The suppression was partial rather than absolute and was critically dependent upon the concentration and time of addition of soluble Con A or Con A-activated spleen cells to the MLC. Suppressive effects of Con-A activated spleen cells were mediated by T cells since suppressor cell activity was abrogated by treatment of spleen cells with anti-θ serum and complement before or after Con A activation. X irradiation of spleen cells before Con A treatment also abrogated generation of suppressor cell activity. After activation by Con A, however, the function of suppressor cells was radioresistant. Although the precise mechanism(s) of suppression is, as yet, unknown, the precursors of CL must be exposed to Con A-activated cells during the early phases of the immune response for suppression to occur. Kinetic studies revealed that suppression of CL responses was not due to a failure to initiate an immune response, but represented a response which developed initially, but subsequently aborted. The relevance of these observations to the concepts of T-cell-T-cell interaction and regulatory control of immune responses by T cells is discussed.