Disparate immunoregulatory potentials for double-negative (CD4- CD8-) alpha beta and gamma delta T cells from human patients with cutaneous leishmaniasis.
Although most T lymphocytes express the alphabeta T-cell receptor and either CD4 or CD8 molecules, a small population of cells lacking these coreceptors, CD4- CD8- (double negative [DN]) T cells, has been identified in the peripheral immune system of mice and humans. To better understand the role that this population may have in the human immune response against Leishmania spp., a detailed study defining the activation state, cytokine profile, and the heterogeneity of DN T cells bearing alphabeta or gammadelta T-cell receptors was performed with a group of well-defined cutaneous leishmaniasis patients. Strikingly, on average 75% of DN T cells from cutaneous leishmaniasis patients expressed the alphabeta T-cell receptor, with the remainder expressing the gammadelta receptor, while healthy donors displayed the opposite distribution with approximately 75% of the DN T cells expressing the gammadelta T-cell receptor. Additionally, alphabeta DN T cells from cutaneous leishmaniasis patients are compatible with previous antigen exposure and recent activation. Moreover, while alphabeta DN T cells from Leishmania-infected individuals present a proinflammatory cytokine profile, gammadelta DN T cells express a regulatory profile exemplified by interleukin-10 production. The balance between these subpopulations could allow for the formation of an effective cellular response while limiting its pathogenic potential.
Antonelli
Lis R V
LR
Department of Biochemistry and Immunology, Federal University of Minas Gerais, and Immunology Service, Hospital Edgard Santos, Bahia, Brazil.
Dutra
Walderez O
WO
Oliveira
Ricardo R
RR
Torres
Karen C L
KC
Guimarães
Luiz H
LH
Bacellar
Olivia
O
Gollob
Kenneth J
KJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta