Mitra D K, De Rosa S C, Luke A, Balamurugan A, Khaitan B K, Tung J, Mehra N K, Terr A I, O'Garra A, Herzenberg L A, Roederer M
Department of Genetics and Allergy Clinic, Immunology Division, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Int Immunol. 1999 Nov;11(11):1801-10. doi: 10.1093/intimm/11.11.1801.
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 (MT(2), CD45RA(-)CD62L(+)CD11a(dim)) or primarily IFN-gamma (MT(1), CD45RA(-)CD62L(-)CD11a(bright)). 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 T(h)1 (dominated by IFN-gamma production) or T(h)2 (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, MT(1) and MT(2). Significantly, the representation of the MT(1) and MT(2) subsets differs dramatically between subjects with tuberculoid leprosy (a T(h)1 disease), or lepromatous leprosy or atopic disease (T(h)2 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.
我们根据CD11a、CD45RA和CD62L的表达确定了CD4记忆T细胞的功能极化亚群。在几个表型不同的CD4记忆细胞亚群中，有两个亚群在受到刺激时主要产生IL-4（MT(2)，CD45RA(-)CD62L(+)CD11a(dim)）或主要产生IFN-γ（MT(1)，CD45RA(-)CD62L(-)CD11a(bright)）。此外，CD4细胞的其他四个表型不同的亚群具有独特的细胞因子谱。为了确定这些细胞类型的代表性的临床相关性，我们分析了患有慢性病麻风病和特应性疾病患者的血液。这些疾病的特征是免疫极化，因为受影响个体中的T细胞反应通常强烈偏向于T(h)1（以IFN-γ产生为主）或T(h)2（IL-4产生）。我们在此表明，这种极化反映了影响记忆CD4 T细胞功能不同亚群MT(1)和MT(2)代表性的稳态或分化机制。值得注意的是，在结核样麻风病（一种T(h)1疾病）、瘤型麻风病或特应性疾病（T(h)2疾病）患者中，MT(1)和MT(2)亚群的代表性有显著差异。然而，当在所有疾病状态的个体之间进行比较时，这些或任何其他精细分辨的CD4亚群的细胞因子谱没有差异。因此，正是外周血中这些亚群的代表性诊断了免疫系统的极化状态。
