Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases.
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.
Mitra
D K
DK
Department of Genetics and Allergy Clinic, Immunology Division, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
De Rosa
S C
SC
Luke
A
A
Balamurugan
A
A
Khaitan
B K
BK
Tung
J
J
Mehra
N K
NK
Terr
A I
AI
O'Garra
A
A
Herzenberg
L A
LA
Roederer
M
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007156:Immunologic Memory; D015440:Leprosy, Lepromatous / Q000276:immunology*; D015441:Leprosy, Tuberculoid / Q000276:immunology*; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines