Contributions of Two Distinct T Cell Subsets (CD4+, CD8+CD60+) to Induction of Specific Memory IgE Responses

Rationale: T cells and their cytokines (IL-4) are required for human IgE responses and phosphorylated p38 MAP kinase (p38MAPK) correlates with IL-4.  We reported that two distinct T cell subsets (CD4+, CD8+CD60+) are required for induction of human specific memory IgE responses (Smith-Norowitz, et al. J. Immunology).  We now report the interrelationships between CD4+ and CD8+CD60+ T cells in induction of these responses.

Methods: Blood/serum was obtained from ragweed sensitized humans (n=6) and CD4+ and CD8+CD60+ T cell expression of p38MAPK (MESF),  CD4+IL-4+ and CD8+CD60+IL-4+ T cell numbers and IgE levels (IU/ml) were determined (flow cytometery, fluoroenzymeimmunoassay). PBMC (1x10⁶) were cultured for 0-12 days ± varying concentrations of ragweed antigen and IgE levels in supernatants determined (ng/ml)(ELISA).

Results: CD4+ and CD8+CD60+ T cells were ~40% and ~5% of blood lymphocytes, respectively.  CD4+ and CD8+ T cell expression of p38MAPK correlated with serum IgE (p=0.001, p=0.005, respectively).  When CD4+ or CD8+CD60+ T cells were depleted before, or anti-IL-4 was included in culture, no specific memory IgE responses were induced; reconstitution of memory IgE responses required bothsubsets.  Of the CD4+ T cells only 5% were CD4+IL-4+, whereas of the CD8+CD60+ T cells, >99% were CD8+CD60+IL-4+ (all were p38MAPK+); the individual T cell subsets (~20,000, 50,000 cells, respectively) did not produce sufficient IL-4 for induction of memory IgE responses by PBMC (1 million cells), but together they did.

Conclusions: Both CD4+ and CD8+CD60+ T cell subsets are necessary to produce sufficient IL-4 required for induction of specific memory IgE responses of ragweed sensitized humans.