Natural effector T lymphocytes in normal mice.

Abstract

The "natural" T-cell activity in normal unimmunized mice was studied. By double-parameter fluorescence-activated cell sorter analysis, it was found that 5-10% of all splenic Lyt-2+ and L3T4+ lymphocytes are large, of which more than half are in mitotic cycle. In contrast with small resting cells of the same phenotype, activated (large) T cells isolated from normal mice are functional effector cells: L3T4+ large cells induce normal B lymphocytes into proliferation and antibody secretion, while large Lyt-2+ cells efficiently suppress B-lymphocyte responses, No effector cell cytolytic activity could be detected among naturally activated T cells. The significance of these findings for the internal activity in the normal immune system is discussed.Much attention has been given in the past to natural antibodies, from both the theoretical (1) and the clinical points of view (2, 3). Astonishingly, the counterpart on the T-cell compartment of such natural activity of B lymphocytes has not been described thus far. The evaluation of current perspectives of an integrated immune system, which implies some degree of autonomous activity (4, 5), led us to investigate the presence of activated T cells in normal animals. The T-cell equivalents of "natural" plasma cells would be effector cells: helper (TH), suppressor (Ts), or cytotoxic T lymphocytes (CTL). The availability of assay systems that selectively detect such effector functions regardless of clonal specificities (6, 7) makes it possible to investigate the presence of those cells. Furthermore, lymphocytes differentiate both in bone marrow and thymus to a resting state of small immunocompetent cells (8,9), allowing the identification of activated cells in the periphery by their presence in the mitotic cycle. We report here that roughly 10o of all T lymphocytes in normal unimmunized mice are large blast cells, of which at least some exert effector functionsnamely, helping or suppressing B lymphocytes. MATERIALS AND METHODSMice. BALB/c mice, kept in conventional specific pathogen-free conditions, were used at ages between 8-12 weeks.Antibodies and Reagents. The following monoclonal antibodies were used with rabbit complement in cytotoxic treatments: rat IgMK, anti-Thy-1, J1J, a kind gift of J. Sprent (Scripps Clinic and Research Foundation, La Jolla, CA); mouse IgMK, anti-Lyt-2.2, HO-2.2 (10); rat IgGK, anti-L3T4, GK-1.5 (11); and mouse IgMK, anti-I-Ab/d, B17-263 (12).These were used as ascitic fluids or culture supernatants at the appropriate dilutions. For immunofluorescence studies, the following biotin-conjugated monoclonal antibodies were used to identify the various lymphocyte classes: rat IgGK, anti-A chain, R33-60 (13); rat IgGK, anti-Lyt-2, 53-6.72 (14); and rat IgGK, anti-L3T4, H-129-19.69 (15). These were used after ion-exchange column purification from culture super- Cell Cultures and Assays. All cultures were set in 0.2-ml flat-bottom microtiter plates as described (16). Growth of purified small and large T lymphocytes was assayed in cultures of 105 cell...

Transplantation tolerance correlates with high levels of T- and B-lymphocyte activity.

“…Selftolerance in normal individuals is likely to be, at least in part, achieved by similar mechanisms. Thus, normal and antigenfree mice contain high numbers of activated B and T cells (33,34). Importantly, CD8' blasts isolated from normal mice are efficient suppressors of B-cell response but lack cytotoxic ability, while helper cells but not inflammatory CD4' cells are naturally activated.…”

Role of Transcriptional Repressor ICER in Cyclic AMP-mediated Attenuation of Cytokine Gene Expression in Human Thymocytes

“…Thymocytes were fractionated over discontinuous Percoll gradients (Amersham Pharmacia Biotech) (28). Cells with densities of 1.060 Ͻ o Ͻ 1.070 and p Ͼ 1.070 were collected and classified into large (significantly enriched for medullary thymocytes) and small (cortical) thymocytes according to an established protocol (7).…”

Naturally activated CD4+ T cells are highly enriched for cytokine-producing cells

“…In contrast, naturally activated CD8 + splenocytes showed suppressive activity, inhibiting the proliferation and Ig secretion of LPS-stimulated B cells [11]. Naturally activated T cells proliferated poorly in response to polyclonal stimuli such as Con A, anti-CD3 antibodies or PMA/ ionomycin, even in the presence of IL-2 [12].…”

“…We found that naturally activated CD4 + T cells are enriched for cells expressing activation markers and producing IL-4, IL-10 and IFN-+ . As demonstrated before [11], the large activated CD4 + T cells are effector helper T cells. We also found that a large proportion of IL-4-and IL-10-producing CD4 + T cells simultaneously produced IFN-+ .…”