Cytotoxicity and weak CD40 ligand expression of CD8+ type 2 cytotoxic T cells restricts their potential B cell helper activity
✍ Scribed by Subash Sad; Lakshmi Krishnan; R. Chris Bleackley; David Kägi; Hans Hengartner; Tim R. Mosmann
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 901 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Department of Biochemistry,
Cytotoxicity and weak CD40 ligand expression of CDS+ type 2 cytotoxic T cells restricts their potential B cell helper activity
Naive CD8' T cells differentiate into distinct cytokine-secreting subsets: T helper (Th)l-like cytotoxicT cells (Tcl) andTh2-like Tc2. AlthoughTh2 cells provide strong B cell help, we show that Tc2 cells secreting the same cytokines provide only modest B cell help for IgM production, and only when large numbers of B cells were stimulated with small numbers of Tc2 cells. Lack of effective B cell help by Tc2 cells was attributable partly to their cytotoxicity towards B cells. Both Tcl and Tc2 cells killed small resting B cells mainly by a perforindependent mechanism. In contrast to normal Tc2 cells, perforin-deficient Tc2 cells failed to kill small resting B cells and induced IgM and IgGl production, although their B cell help was significantly lower than that mediated by Th2 cells. This may be partly attributable to the ability of Tc2 but not Th2 cells to kill activated B cells even in the absence of perforin. Plate-bound antLCD3 antibodies inhibited Tc2 killing of B cells and induced substantial immunoglobulin production. Additionally, Tcl and Tc2 cells failed to express CD40 ligand (CD4OL), whereas Thl and Th2 cells expressed high levels of CD40L. Stimulation of Tcl and Tc2 cells with plate-bound anti-CD3 antibodies for extended periods resulted in low-level expression of CD40L. Proliferation of small resting B cells correlated with immunoglobulin production: proliferation was promoted strongly by Thl and Th2, weakly by normal Tcl and Tc2, and moderately by perforin-deficient Tcl and Tc2 cells. Thus, Tc2 cells may not contribute significantly to cognate B cell help during normal responses.