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Two Distinct T Cell Subsets, CD4⁺ and CD8⁺CD60⁺, and Their Cytokines Are Required for In Vitro Induction of Human Ragweed-Specific Memory IgE Responses

Tamar A. Smith-Norowitz^1,*,, Jonathan Silverberg, Kevin B. Norowitz, Martin H. Bluth^*,, Seto Chice, Rauno Joks^*,¶, Maja Nowakowski^*, and Helen G. Durkin^*,

^* Center for Allergy and Asthma Research at State University of New York Downstate and Department of Pediatrics, Department of Pathology, Department of Surgery, and ^¶ Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY 11203

CD8⁺CD60⁺ T cells (80–98% CD45RO⁺; 20% CD23⁺) are significantly increased in the blood of serum IgE⁺ ragweed-sensitized (RS) compared with serum IgE-nonatopic humans (p = 0.001). CD8⁺CD60⁺ T cells of the RS patients produced IL-2, IL-4, IL-10, IL-12, IFN-. and IFN-, but not IL-6 or IL-13. When their PBMC were cultured with ragweed Ag (RA), peak IgE responses occurred on day 10; none was induced with non-cross-reacting or without Ag; nonatopic PBMC did not respond to any stimulant. When either CD4⁺ or CD8⁺CD60⁺ T cells were depleted from RS PBMC before culture with RA, no IgE responses were induced. If purified CD4⁺ T cells or low numbers of CD8⁺CD60⁺ T cells were added back to the depleted PBMC, IgE responses were restored. However, higher numbers of CD8⁺CD60⁺ T cells totally suppressed IgE responses. Total suppression also was obtained when RS PBMC were cultured with RA and either anti-IL-2, IL-4, IL-10, IL-12, IFN- (all concentrations), or IFN- (low concentrations), but not anti-IL-6 or IL-13. Higher concentrations of anti-IFN- potentiated IgE responses.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Tamar A. Smith-Norowitz, Department of Pediatrics, State University of New York Downstate Medical Center, Box 49, 450 Clarkson Avenue, Brooklyn, New York 11203. E-mail address: tamar.smith-norowitz{at}downstate.edu

² Abbreviations used in this paper: BPO, benzylpenicilloyl; KLH, keyhole limpet hemocyanin; RS, ragweed sensitized; NA, nonatopic; ECD, PE-Texas Red; NGS, normal goat serum.