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International Immunology, Vol. 11, No. 11, 1801-1810, November 1999
© 1999 Japanese Society for Immunology

Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases

Dipendra K. Mitra1,3, Stephen C. De Rosa1, Andrew Luke2, Arumugam Balamurugan3, Binod K. Khaitan4, James Tung1, Narinder K. Mehra3, Abba I. Terr2, Anne O'Garra5, Leonore A. Herzenberg1, Leonard A. Herzenberg1 and Mario Roederer6

1 Department of Genetics and
2 Allergy Clinic, Immunology Division, Department of Medicine, Stanford University, Stanford, CA 94305, USA
3 Histocompatibility & Immunogenetics Department and
4 Department of Dermatology, All India Institute of Medical Sciences, New Delhi 110029, India
5 Department of Immunobiology, DNAX Research Institute, Palo Alto, CA 94304, USA
6 Department of Stomatology, San Francisco, CA 94143-0422, USA

Correspondence to: M. Roederer, Department of Stomatology, 521 Parnassus Ave C634C, San Francisco, CA 94143-0422, USA

We identified functionally polarized subsets of CD4 memory T cells on the basis of the expression of CD11a, CD45RA and CD62L. Within the several phenotypically distinct subsets of CD4 memory cells are two that, upon stimulation, produce primarily IL-4 (MT2, CD45RACD62L+CD11adim) or primarily IFN-{gamma} (MT1, CD45RACD62LCD11abright). In addition, four other phenotypically distinct subsets of CD4 cells have unique cytokine profiles. To determine the clinical relevance of the representation of these cell types, we analyzed blood from patients with the chronic diseases leprosy and atopy. These diseases are characterized as immunologically polarized, since T cell responses in affected individuals are often strongly biased towards Th1 (dominated by IFN-{gamma} production) or Th2 (IL-4 production). We show here that this polarization reflects homeostatic or differentiation mechanisms affecting the representation of the functionally distinct subsets of memory CD4 T cells, MT1 and MT2. Significantly, the representation of the MT1 and MT2 subsets differs dramatically between subjects with tuberculoid leprosy (a Th1 disease), or lepromatous leprosy or atopic disease (Th2 diseases). However, there was no difference in the cytokine profiles of these or any of the other finely resolved CD4 subsets, when compared between individuals across all disease states. Thus, it is the representation of these subsets in peripheral blood that is diagnostic of the polarized state of the immune system.

Keywords: cytokine profile, flow cytometry, intracellular cytokine staining, Th1, Th2

Transmitting editor: R. Hardy


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