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Updated: Aug 8, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Modulation of murine in vitro immune response by verapamil (V)
A B Singh1, K Hiehle, P Casale
1Division of Nephrology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019.
Insights
Calcium influx is crucial for activating cytotoxic T lymphocytes (CTL) and B cells, but not suppressor cells. Verapamil, a calcium channel blocker, selectively inhibits CTL and B cell induction, highlighting differential calcium dependency in lymphocyte activation.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Lymphocyte activation requires specific signals, with transcellular calcium influx being critical in some cases.
- The role of calcium in activating all lymphocyte subsets is not fully understood.
Purpose of the Study:
- To investigate the effect of the calcium channel blocker verapamil on the induction of murine cytotoxic T lymphocytes (CTL), suppressor cells, T helper cells, and B cells.
- To determine the selective role of calcium in lymphocyte activation.
Main Methods:
- Treatment of murine lymphocytes with verapamil (V).
- Assessment of the induction of CTL, suppressor cells, T helper cells, and B cells.
- Evaluation of verapamil's synergy with cyclosporin A (CsA) and reversal by exogenous helper factors.
Main Results:
- Verapamil inhibited the induction of cytotoxic effector cells, acting on the afferent immune response limb.
- Verapamil synergized with CsA and its effects were reversible with helper factors.
- Verapamil inhibited B cell proliferation without T cell help but did not inhibit B cell activation or suppressor cell induction.
Conclusions:
- Calcium plays a selective role in lymphocyte activation, being essential for CTL and B cell induction but not suppressor cell induction.
- Verapamil's selective suppression provides insights into the differential activation requirements of various lymphocyte subsets.
Abstract:
Functionally distinct lymphocyte subsets differ with regard to necessary activation signals. In selected circumstances lymphocyte activation has been shown to be critically dependent upon transcellular calcium influx. Whether calcium plays a central role in the activation of all lymphocytes remains to be determined. The effect of the calcium channel blocker verapamil on the induction of murine cytotoxic T lymphocytes (CTL), suppressor cells, T helper cells, and B cells was investigated. Verapamil (V) was found to inhibit the induction of cytotoxic effector cells. V acted primarily on the afferent limb of this immune response, was synergistic with cyclosporin A (CsA), and its effects could be largely reversed by the addition of exogenous helper factors. V also inhibited B cell proliferation in response to anti-mouse IgM in the presence of 2-mercaptoethanol, but in the absence of cognate or non-cognate T cell help. In contrast to this, V did not inhibit the activation of cells capable of inducing B cell proliferation nor did it inhibit the induction of suppressor cells. The selective suppression of V is discussed in terms of activation requirements of CTL, suppressor cells and helper cell subsets.
